路漫漫其修远兮分享 http://blog.sciencenet.cn/u/zhpd55 追求科学,勇于探索,苦海无涯,愿作小舟。

博文

同时测试数千种化合物以发现新药和量身定制的治疗方法

已有 1147 次阅读 2025-1-29 18:23 |个人分类:药物动态|系统分类:海外观察

同时测试数千种化合物以发现新药和量身定制的治疗方法

诸平

 Drug-Development-AI-Data-Concept-777x518.webp.jpg

Fig. 1 Researchers at the University of Basel have developed a method to simultaneously test the effects of over 1,500 active substances on cell metabolism. This innovative approach has revealed previously unknown mechanisms of action for existing medications.Credit: SciTechDaily.com

 High-throughput_1000x500.jpg

Fig. 2 How exactly do drugs affect the metabolism of cells? Researchers are investigating this question with a new high-throughput method - testing thousands of compounds at once. (Image: Adobe Stock, KI)

瑞士巴塞尔大学University of Basel, Basel, Switzerland20251月28日提供的消息,同时测试数千种化合物以发现新药和量身定制的治疗方法Testing Thousands of Compounds Simultaneously to Uncover New Drugs and Tailored Treatments)。

科学家们公布了一种突破性的方法来测试数千种活性物质如何同时影响细胞代谢。Scientists have unveiled a groundbreaking method to test how thousands of active substances influence cellular metabolism simultaneously.

通过使用高通量代谢组学(high-throughput metabolomics )和质谱法(mass spectrometry),他们发现了现有药物的意想不到的效果,为重新利用药物和加速药物发现铺平了道路。有朝一日,这种方法可以将患者特定的代谢数据与量身定制的治疗方法结合起来。

了解活性物质和细胞代谢Understanding Active Substances and Cell Metabolism

活性物质如何影响细胞的代谢过程?回答这个问题可以为开发新药提供有价值的见解。然而,研究化合物库如何与细胞代谢相互作用历来是一项资源密集型任务。

现在,来自巴塞尔大学生物医学系(Department of Biomedicine, University of Basel, Basel, Switzerland)的研究人员介绍了一种突破性的方法,可以同时测试数千种物质的代谢影响。

他们的发现基于一种被称为高通量代谢组学的技术,相关研究结果于2025128日已经在《自然生物技术》(Nature Biotechnology)杂志网站发表——Laurentz SchuhknechtKarin OrtmayrJürgen JänesMartina BläsiEleni PanoussisSebastian BorsTerézia DorčákováTobias FuhrerPedro Beltrao, Mattia Zampieri. A human metabolic map of pharmacological perturbations reveals drug modes of action. Nature Biotechnology, 2025. DOI: 10.1038/s41587-024-02524-5.Published: 28 January 2025. 

参与此项研究的有来自瑞士巴塞尔大学(Department of Biomedicine, University of Basel, Basel, Switzerland)、瑞士苏黎世联邦理工学院分子系统生物学研究所(Institute of Molecular Systems Biology ETH Zürich, Zürich, Switzerland)、奥地利维也纳大学生命科学学院(Department of Pharmaceutical Sciences, Faculty of Life Sciences University of Vienna, Vienna, Austria)、瑞士生物信息学研究所(Swiss Institute of Bioinformatics, Lausanne, Switzerland)的研究人员。

预测副作用和药物相互作用Predicting Side Effects and Drug Interactions

当我们更好地了解活性物质如何干预细胞代谢时,药物的开发可以加速,马蒂亚·赞皮耶里教授(Professor Mattia Zampieri)解释说。我们的方法提供了这些活性物质的额外特征,从中我们可以推断可能的副作用或与其它药物的相互作用。

由该研究论文的第一作者劳伦兹·舒克内希特(Laurentz Schuhknecht)博士领导的研究人员,在细胞培养板上的数千个小孔中培养细胞。然后,他们用化合物库中的1500多种物质中的一种处理每个孔中的细胞,并使用一种称为质谱法的方法来测量细胞内数千种小生物分子(称为代谢物)在处理后的变化。

这使得研究小组能够收集到每种活性化合物在细胞中超过2000种代谢产物变化的数据。然后,他们将这些变化与未经处理的细胞通过计算机辅助分析获得的变化进行了比较。这导致了对每种活性物质对细胞代谢的影响的概述,使得研究人员对其各自的作用方式有了非常准确的了解。

药物机制的惊人发现Surprising Discoveries in Drug Mechanisms

市售药物对细胞代谢的影响比我们想象的要大得多,马蒂亚·赞皮耶里教授在总结实验结果时说。特别值得注意的是以前不为人知的普通药物的作用方式。例如,研究小组发现,用于治疗一种涉及甲状腺功能的罕见疾病的药物替拉替醇(tiratricol),除了其主要作用方式外,还会影响某些核苷酸(nucleotides)的产生,而核苷酸是DNA合成的基石

劳伦兹·舒克内希特说这种药物因此可能成为一个新的应用领域的一个很好的候选者:调节核苷酸的生物合成,并因此被用于癌症治疗,以抑制肿瘤的生长。

利用数据进行人工智能驱动的药物设计Leveraging Data for AI-Driven Drug Design

从这种高通量方法中获得的综合数据可以帮助训练人工智能来设计新药物。马蒂亚·赞皮耶里说:我们的长期愿景是将疾病的患者特异性代谢特征与数千种候选化合物的代谢干扰模式相匹配,来揭示能够逆转由疾病引起的分子变化的最佳药物。

药理学家强调,为了更接近这一愿景,不仅重要的是了解物质对代谢的作用。同样重要的是人体如何处理这些活性物质,从而如何改变它们的作用。因此,科学家们正在进行进一步的研究,以更密切地检查人体与活性物质之间的相互作用。

本研究得到了NCCR抗抵抗项目{NCCR AntiResist project funding (180541)}、瑞士国家基金{Schweizerischer Nationalfonds简称SNF, SNF Sinergia (CRSII5_189952)}、诺华研究基金会{Novartis Forschungsstiftung (FN24-0000000612)}、美国国立卫生研究院研究项目{NIH Research Project (R01) (1R01AI173328-01)}、德西蕾和尼尔斯·伊德基金会{Desirée and Niels Yde Foundation (543-23)}、苏黎世联邦理工学院研究基金ETH research grant (ETH-33 19-2)}、瑞士癌症联盟{Krebsliga Schweiz (KLS-4124-02-2017)}、赫尔穆特·霍顿基金会Helmut Horten Stiftung以及苏黎世联邦理工学院基金会ETH Zurich Foundation)的资助

上述介绍仅供参考,欲了解更多信息敬请注意浏览原文相关报道

Testing the effect of thousands of compounds on cellular metabolism

Abstract

Understanding a small molecule’s mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines. By testing more than 3.4 million drug–metabolite dependencies, we generated a lookup table of drug interference with metabolism, enabling high-throughput characterization of compounds across drug therapeutic classes in a single-pass screen. The identified metabolic changes revealed previously unknown effects of drugs, expanding their MoA annotations and potential therapeutic applications. We confirmed metabolome-based predictions for four new glucocorticoid receptor agonists, two unconventional 3-hydroxy-3-methylglutaryl-CoA (HMGCR) inhibitors and two dihydroorotate dehydrogenase (DHODH) inhibitors. Furthermore, we demonstrated that metabolome profiling complements other phenotypic and molecular profiling technologies, opening opportunities to increase the efficiency, scale and accuracy of preclinical drug discovery.



https://blog.sciencenet.cn/blog-212210-1470892.html

上一篇:模糊固体和液体界限的革命性材料——一种新型物质
下一篇:超薄吸收器打破纪录,彻底改变能量和隐身
收藏 IP: 111.20.218.*| 热度|

1 郑永军

该博文允许注册用户评论 请点击登录 评论 (0 个评论)

IP: 130.219.8.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [11][婵炴挾枪椤撶婵炴挾枪椤擄拷   2010-10-19 22:01
闂侇叏绲肩花铏规嫚绾惧鈧挳鎮介妸銈堝幀闁搞儲鍨濆Ч澶愬磻濮橆剛姣堥柣褌绮欑槐鍫曟儍閸曨喖鐒归悷灏佸亾闁告瑯鍨禍鎺撳閹寸姷鍘介柕鍡嫹

濞戞挸顑夊ḿ浼村及椤栨繂鈧挳宕烽敓锟�1999妤犵偟顥愰獮蹇擃嚗濡ゅ啯鐣盢IH Grant闁汇劌瀚幉宕囨啺娓氬﹦绀夐柛娆樺灟娴滄帡鎯囩€n亜姣夐柛锔哄妽椤掓繃绋婄€n亜顤呭ù鐘崇墧缁楀绂掗崨顓炲殥缂備礁绻愬﹢顏嗙礃鎼粹剝绂囬柛瀣亢缁诲啴宕濋妸褍鈷栭悹鍥ㄦ礋閻涙瑩鏁嶅畝鍐e亾鐏炶偐鐟ù鐘崇墳缁绘洟宕戝宕囩畺濞存粣鎷�14濞撴艾顑囧鐐閹巻鍋撻敓锟�

http://www.researchgrantdatabase.com/g/5R01DK053063-05/SKIN-CNS-BLADDER-REFLEX-ARC-FOR-MICTURITION-AFTER-SCI/

SKIN-CNS-BLADDER REFLEX ARC FOR MICTURITION AFTER SCI

Chuan-guo Xiao
New York University School Of Medicine New York, Ny 10016

Grant 5R01DK053063-05 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ZRG1

Abstract: The neurological bladder caused by spinal cord injury (SCI) presents a significant medical and social problem. There is no satisfactory treatment yet. Supported by the Paralyzed Veterans of America and NIH, a new reflex pathway, "Skin-CNS-Bladder" for controlled micturition after SCI has been successfully established in rat, cat and canine models. Preliminary clinical application of 14 SCI patients also provided very promising results. The study proposed here is to transfer the Skin-CNS-Bladder reflex functions. The ventral root (VR) of a lumbar nerve (L5) below the spinal cord lesion will be anastomosed to the sacral VR (S2 and/or S3) which innervate the bladder, while leaving the intact L5 dorsal root (DR) as a started of micturition. After the axonal regeneration, controllable voiding would be initiated by scratching the L4 dermatome. Effect of the new reflex pathway on bladder function will be evaluated by means of electrophysiology and urodynamics. Its effect on bowel and sexual functions will also be studied. The procedure may revolutionize the treatment of neurogenic bladder after SCI, It requires relatively minor surgery on 2 paralyzed nerves. It does not involve implantation of electrodes or other devices but provides unique voluntary control of bladder emptying. Scientifically, the study will further prove the new concept derived from the unique somatic-autonomic reflex that the impulses delivered from the efferent neurons of a somatic reflex arc may be transferred to initiate response of an autonomic effector. This new concept may be widely useful, not only for neurogenic bladder, but also for other problems caused by the spinal cord injury or diseases.

Keywords: electrophysiology, human therapy evaluation, neurogenic urinary bladder disorder, neuroregulation, neurosurgery, somatic reflex, spinal cord injury, urination, central nervous system, clinical trial, functional ability, outcomes research, quality of life, skin, urinary electronic stimulator, clinical research, human subject

Project start date: 1999-09-30

Project end date: 2007-12-31

5R01DK053063-05 (2004): $642796
IP: 69.117.13.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [10][婵炴挾枪椤撶婵炴挾枪椤擄拷   2010-10-19 09:16
13婵°倛澹堢换鏍矓瀹ュ棗澹栧☉鎾崇Т瑜版煡宕f繝鍕暠濞存粌鎼悿鍕捶閵婎煈鍞ㄥù婊冩惈瑜板牊绋夊鍕晩.闁煎弶鐗滃▓鎴﹀箥鐎n偅閽╅柡鍐f櫅濮樸劑宕戝宕囩畺濞存粌妫楁慨鈺呮偋閳轰胶鏉藉Δ鐙呮嫹,濞戞挻娼欑花銉ф嫚閺囥垻宕�,妤犵偞婀圭悮鍗炩枎閿涘嫮鐥呴柛銉ㄦ椤斿秹鏌庨弶鎴犳毎閻炴凹鍋呮竟鎺楀礄閸℃洜鍩冨ù鐘劜鐢綊鐛敓锟�,閺夆晝鍋犵换鏍ㄧ▔椤忓懏浠橀柛鈺冨劋濠€浼存儍閸曨亞鐨戦悗鍦仱閸忔ɑ绋夐埀顒勫籍閻樺啿顣查柣顓ㄦ嫹,閻忕偛鎳愰崝褏浜告潏銊﹂檷闁哄嫮鍋撻幉婊勭閺嶎厼浜濋柤灞傚劚閵囧洭鎯冮崟顔碱棇闊浄鎷�.

濠碘€冲€归悘澶嬫媴閻樺搫绐涢柣銈嗗灥濞存鈧懓鐖兼竟宀€鈧纰嶅﹢渚€姊婚鈧。锟�,闁告瑯鍨禍锟�,濞达絽妫濋崑鍛村及椤栨艾缍楀鑸电墧缁斿瓨绋夐鍫燂紪濡府鎷�,濠㈠爢鍐惧晙闁告瑯鍨禍鎺楀箺閸℃洜鐨戦悗鍦仩椤斿鏌嗛幘鑸靛€炵紓浣堝懐鏁鹃悹浣靛姀椤旓拷.闁告瑯鍨紞妯绘交閻愯尙鍞ㄩ柡鍫墰濞堟垿骞嗛崨顓炴瀸闂侇喗鍨濈粭澶嬬閸℃锟�,閻忓繗椴稿ḿ鐢稿矗閹达絻鈧啯鎷呴悩鍨暠濡ゅ倹枪椤拷,閻忕偞娲滈妵姘媴閻樺灚鐣遍柤璇″灠缁猴拷,闂侇叏绲肩粭澶愬及椤栨粎鎳呴悹鍥ㄧ箑缁狅拷?

濞戞搩鍘煎ù妤佹交濞嗗酣鍤嬬紒鈧崣銉х獥,閻庡湱鍋涘﹢顏堝及椤栨稒锟ラ柣顓滃劤濞堟垿骞囧顓犳瘜濠㈤浜滈ˇ锟�,闂侇偆濮甸崹姘交濞嗘劗澹夐柣銊ュ閻剟妫冮敓锟�,濠殿垱甯婄紞瀣嫉婢跺鐟濋柛娆樺灡鐢綊宕¢崫銉︾暠閻犳劧绲奸幑锟�.
IP: 113.142.233.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [9]jihua0a   2010-10-15 12:25
缂傚洤楠稿ù妤佺妤﹁法妲戝ù鐘垫焿閸婂瓨瀵奸悩鍙夌闁汇劌瀚晶婊堝嫉閿燂拷
閻熸瑤寮搕tp://video.sina.com.cn/v/b/38888027-1808244527.html
IP: 202.113.9.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [8]goudan1   2010-10-13 16:50
闁规鍨辩拹锟�,闁煎弶鐗曢惃顒冪疀閸涙番鈧繒绱掕箛姘辩畺闁告柣鍔庢晶锟�,濞存粏妗ㄧ紞瀣偓鍦仱閻涙瑩宕ユ惔陇瀚欓柤鎯у槻閸n垶骞嶅鍫濆幋閹煎瓨姊婚弫銈嗙鎼粹€抽瀺闁汇倧鎷�,濞寸姴楠搁悾鐘垫偘鐏炶壈绀嬮柛娆樺灟娴滄帞鈧懓鑻崣蹇涘及鎼达絾顏ら悗鐟板暢閸撳磭鈧稒鍔欓崳鐑藉传椤忓懏绠掗柛鎺濆亗濮瑰顫㈢紒妯汇仧,闁煎瓨鍨甸悺娆撴煂鐏炵偓笑闂傚嫨鍨归敍锟�, 闁瑰嘲銇樼粭澶愬礆娴煎瓨鐝滃璇″亜濮樸劍鎷呭⿰鍕缁炬澘绉崇花銊╂儍閸曨亝鐪�,
IP: 210.77.95.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [7]闂傚嫯娉涢〃锟�   2010-10-13 08:50
闁兼澘鍟块幆锟�
闁活亣澹堥~锟�
濞戞挸绉撮幆锟�
濞戞挸绉烽~锟�
IP: 218.199.39.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [6]閻犱礁鎲$粋瀣交閿燂拷   2010-10-13 05:43
闁告艾鏈崜鎵磾閹存繂鍑爓c101闁汇劌瀚﹢鍛枖閺囶亞绐楅柡鍌滎攰閸ㄩ鈧稒鍔曞﹢顏堝箥閹惧厖娴烽柣銊ュ濡埖锛愬Ο鍦憪闁炽儲绮堢花鈺呭礂椤愩垻纾婚柍銉︾箖閸ㄣ劑鍨惧⿰鈧粭浣圭▔閸愩劎纾婚柍銉︾箰缁辨繈宕濋悢鎯扮濞戞挻鐪归埀顒婃嫹
IP: 218.199.39.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [5]閻犱礁鎲$粋瀣交閿燂拷   2010-10-13 05:42
闁哄倻顢婇崹椋庘偓娑欏姇濠€顏堝箥閹惧厖娴烽柣銊ュ濡埖锛愬Ο鍦憪闁炽儲绮堢花鈺呭礂椤愩垻纾婚柍銉︾箖閸ㄣ劑鍨惧⿰鈧粭浣圭▔閸愩劎纾婚柍銉︾箰缁辨繈宕濋悢鎯扮濞戞挻鐪归埀顒婃嫹
IP: 123.151.32.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [4]tuner   2010-10-12 23:02
闁瑰瓨鍨肩换鏍ㄧ▔椤忓嫷妯嗛悶娑樼灱閹﹦鎲撮敐鍛唨閻忓繐瀚慨顒勬晬閿燂拷

闁诡噯缍€閳ь剙鎳忓﹢鎶藉礈瀹ュ懐鏆氶柛蹇嬪妽閻ュ懘寮垫径瀣瑩閻忓繑瀵ч崝鍛喆婢舵稓绀夐梻鍥e亾閻熸洑绀侀悾楣冨籍閼搁潧鐨ㄩ柛妯侯儓閸氬倿鏌堥妸锕€绗撻悘蹇氾骏閳ь剙鍊界换鏍ㄥ濮樿京鑸堕柛鎰嚀閸撲即宕抽妸銉ф毉闂侇偆濮甸崹姘嚗閸繍妯嬮梻鍌ゅ櫍椤d粙濡撮敓锟�

闁规亽鍎扮花锟犲矗瀹ュ懐娈哥€殿啫鍐╁€甸柨娑樼灱閺併倝宕氶悜妯艰礋濠㈠爢鍡楁偑闁活煈鍠涢崑鍡涙儍閸曨偄顫炴繛澶嬫磻閸烆剟寮存径鍝ュ晩闁规悶鍊曠敮鍥嚈瑜版帒鍔ラ柟鐑樺笒缂堥亶濡撮崒婊勬殸濞存粌楠搁悾鐘绘儎鐎涙ê澶嶅ù锝嗙矌閺併倖绂嶆惔銈呮暏闁煎疇浜▓鎴犵矈閻愮數鐥呯紒顖濆吹缁椽鏁嶇仦鐓庘枏鐎电増顨夐崬銊╂嚄鏉堛劍鏆紓鍌楁櫔缁辨繄浜搁崸妞惧闁瑰灚鎸哥槐鎴︽晬鐏炶偐鐟濈憸鏉垮船閹肩兘宕楃捄铏规殜闁革絻鍔岄悾濂稿Υ閸岀偞鐝熸慨婵勫€涢埀顒€鑻ˇ濠氭晬鐏炶姤绀堝☉鎾规〃閼垫垿寮搁姀銏╂缂備礁绻愰懟鐔封柦閳╁啫澶嶉梺顐g啲缁辨繈鎯€閸涱剚鐪介弶鈺偵戝Σ鍛婄▔瀹ュ嫮绐楅柡鍫濐槸缂堥亶骞囬悤鍌滅濞戞挸绉撮悾楣冨籍閼搁潧绗撻悘蹇氭硶濞堟垹鎷犲┑鎾剁闁煎灈鍋撻柤瀹犻哺瀵勭閸℃洜鐭濋柣鎺撴构缁变即寮垫径濠勫嫎濞戞挸绉烽崵婊勭▔缂佹ê绗撻柛鎴炰航閳ь剨鎷�

闁告瑥绉撮惃鐘差嚕瑜斿〒鍓佹啺娴i顏辨繛鍫濈仛濡炲倿姊荤€涙ê顤呴梻鈧幐搴$亣闁挎稑鑻崺鈥斥攽閳ь剟鎯冮鍨簽闁圭儤甯掔紙杈ㄦ交濞嗘埈娼氶柣妤勵潐閻b晠鎯冮崟顒佺厵婵炲娲戠弧鍐閳ь剛鎲版担绛嬪敳缂備礁鍟ㄩ埀顒€鍊规晶宥嗙閵夘垳绀夐柟鎭掑劙缁繝宕e鍛鐎殿啫鍐ㄧギ濞达絾瀵ч崹姘跺礉閻曞倻绀夐柟顕嗙秬閳ь剙鎳愬▓鎴﹀箳閹烘垹鍕樺ù鐘茬Ф閸斞勭▔鎼淬埄鍔€閻㈩垶鏅插Ч澶愬嫉婢跺﹦鍙戝鍫嗗倻鐟濋柛姘焿缁辨繈骞掗幒鎴犲嫎闁汇劌瀚弲銉╁几濠娾偓缁″啯瀵煎顓熺畳鐎瑰壊鍠栫槐鎾诲Υ閸屾稑顣查悹瀣尨閳ь剚绮忛崵婊勭▔缂佹ê绗撻悘蹇撶氨閳ь剚绻愮槐婵堜焊鏉堛劍笑闁革负鍔嶉惀鍛村嫉婢跺﹦鍕橀柟鏉跨箳濞堟垿骞嗛崨顓炴瀸濞戞挸顑勭€靛矂宕濋妸銉ф毎闁哄啳鍩栫敮鎾朵焊鐟併倐鍋撻敓锟�
IP: 166.111.107.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [3]闁藉嫸绲芥刊顕€寮堕敓锟�   2010-10-12 21:51
jiangjinsong閻忓繐妫欓崑宥夋儍閸曨剚鐎紒鏃傚У鐢綊鏌呮担绋跨厒濞寸姷澧楀﹢婊堝及閻旇 鏁�,
IP: 221.239.91.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [2]闁兼枼鈧厖娣繛澶涙嫹   2010-10-12 21:01
闁活亜顑勭花锟犳煣閻愵剙澶嶉梺鎻掔灱濞堟垹鎮伴妸锔惧闁挎稑鑻欢銏ゅ籍閻樹警鍤旈柕鍡楀€风紞姗€宕楅崼婵嗙闁活亜顑囧﹢鍛村棘鐟欏嫭笑闁诡剙绨肩粻鐐垫喆閿濆娅炴繛灞稿墲濠€浣圭▔閳ь剚绗熺€n偄鐏囬柛鏃傚枔濞堟垿濡撮敓锟�
IP: 221.239.91.*   | 閻犙嶆嫹 閻犙嶆嫹 +1 [1]闁兼枼鈧厖娣繛澶涙嫹   2010-10-12 20:39
闁哄倸缍婇崑鍛綇绾拋鍤涙繛灞稿墲濠€浣圭▔閳ь剚绗熺€n偄鐏囬柛鏃傚櫐缁辨繈鎳撳畝鍐ㄢ偓瀛樻交濞嗘帞鐝堕悹鍥锋嫹80%闁靛棗鍊风悮閬嶆嚀閸涱垱绁茬€瑰壊鍠楅悗顒佸緞瑜嬮埀顒€鍊瑰Λ锕傛倿閹澘鈧挳寮垫径濠傚笭閻℃帒纾▓鎴犵矓閹寸姷鍩$紓浣哥箺閸ㄥ倿鏁嶇仦鐣岀处閻犱緡鍠涢崐瀵糕偓浣冾潐婢у秹寮垫径灞锯挄濞存粏娅e▓鎴﹀箥鐎n偅閽╅悷娆忔椤e墎鈧稒蓱閵嗗倿鏁嶉崼婵嗚濞寸姰鍎扮划鐘绘偝閺夋寧韬€殿喒鍋撳┑顔碱儜缁辨岸鏁嶅☉娆愪粯闁告艾楠搁惃銏ゆ嚄閽樺妾柟鍨劤閸╁矂鎯冮崟顓熲挄濞存粍妞介崗姗€骞嶉幆褍鐓傞柨娑樼灱缁儤绋夐埀顒勫礆閺夊灝顕ㄥù婊庡墰閳ユḿ鎷嬮妶蹇曠闁烩晠鏅叉穱濠冪▔鏉炴壆鍟婇弶鈺傜懁濞嗐垺绂嶇€n偄鍓伴柤鐚存嫹100濞戞挸娲f禍鎺撶▔婵犲嫭鐣辩€瑰壊鍠楀鍓ф嫻绾懐绠烽柡鍕靛灠閳ь剛鍘х欢閬嶆儍閸曗斁鍋撻崒娑欙骏閻犲鎸搁崯鈧ù鐘劚婢х娀鏌囬敐鍕杽濠㈣埖鑹鹃崟楣冩焽閿濆棛澹夐柛姘悁缁楀懘宕㈢拋宕囧晩闁靛棴鎷�

闁告鐭€靛矂宕堕悙宸Щ闁挎稒纰嶉弻鐔兼焽閿濆牏鐝堕柣銊ュ閸嬪懘鎳撻崨鎵闁哄被鍎撮妴鍐捶閵娿劎绠归梺鎻掔焿缁辨繃鎷呴悩鍝勬鐎规瓕浜﹢鍛存晬濮濃暟tp://www.sciencenet.cn/m/user_content.aspx?id=368948

1/1 | 闁诡剚妲掗锟�:11 | 濡絾鐗犻妴锟� | 濞戞挸锕g粩瀛樸亜閿燂拷 | 濞戞挸顑勭粩瀛樸亜閿燂拷 | 闁哄牜鍋婇妴锟� | 閻犲搫鐤囧ù锟�

Archiver|手机版|科学网 ( 京ICP备07017567号-12 )

GMT+8, 2025-2-19 13:21

Powered by ScienceNet.cn

Copyright © 2007-2025 中国科学报社

返回顶部