全文获取类型
收费全文 | 4188篇 |
免费 | 547篇 |
国内免费 | 302篇 |
出版年
2024年 | 18篇 |
2023年 | 152篇 |
2022年 | 171篇 |
2021年 | 210篇 |
2020年 | 218篇 |
2019年 | 219篇 |
2018年 | 181篇 |
2017年 | 162篇 |
2016年 | 163篇 |
2015年 | 176篇 |
2014年 | 220篇 |
2013年 | 333篇 |
2012年 | 164篇 |
2011年 | 190篇 |
2010年 | 130篇 |
2009年 | 208篇 |
2008年 | 215篇 |
2007年 | 193篇 |
2006年 | 194篇 |
2005年 | 234篇 |
2004年 | 202篇 |
2003年 | 152篇 |
2002年 | 120篇 |
2001年 | 75篇 |
2000年 | 78篇 |
1999年 | 53篇 |
1998年 | 56篇 |
1997年 | 47篇 |
1996年 | 36篇 |
1995年 | 33篇 |
1994年 | 37篇 |
1993年 | 30篇 |
1992年 | 19篇 |
1991年 | 18篇 |
1990年 | 25篇 |
1989年 | 19篇 |
1988年 | 14篇 |
1987年 | 23篇 |
1986年 | 12篇 |
1985年 | 32篇 |
1984年 | 23篇 |
1983年 | 17篇 |
1982年 | 21篇 |
1981年 | 24篇 |
1980年 | 17篇 |
1979年 | 18篇 |
1978年 | 27篇 |
1977年 | 23篇 |
1976年 | 12篇 |
1975年 | 13篇 |
排序方式: 共有5037条查询结果,搜索用时 15 毫秒
991.
The coiled coil structural motif consists of alpha helices supercoiling around each other to form staggered knobs‐into‐holes packing. Such structures are deceptively simple, especially as they often can be described with parametric equations, but are known to exist in various conformations. Even the simplest systems, consisting of 2 monomers, can assemble into a wide range of states. They can form canonical as well as noncanonical coiled coils, be parallel or antiparallel, where helices associate with different degrees of shift, tilt, and rotation. Here, we investigate the energy landscape of heterodimeric coiled coils by carrying out de novo folding simulations starting from amino acid sequence. We folded a diverse set of 22 heterodimers and demonstrate that the approach is capable of identifying the atomic details in the experimental structure in the majority of cases. Our methodology also enables exploration of alternative states that can be accessible in solution beyond the experimentally determined structure. For many systems, we observe folding energy landscapes with multiple energy minima and several isoenergetic states. By comparing coiled coils from single domains and those extracted from larger proteins, we find that standalone coiled coils have deeper energy wells at the experimentally determined conformation. By folding the competing homodimeric states in addition to the heterodimers, we observe that the structural specificity towards the heteromeric state is often small. Taken together, our results demonstrate that de novo folding simulations can be a powerful tool to characterize structural specificity of coiled coils when coupled to assessment of energy landscapes. 相似文献
992.
二氢黄酮醇 4 还原酶在花青素合成中的功能及调控研究进展 总被引:1,自引:0,他引:1
植物色素主要有花青素、类胡萝卜素和生物碱类色素三大类,其中花青素是决定大部分被子植物组织或器官颜色的重要色素。花青素通过类黄酮途径合成,该途径是生物学上研究较多且较为清楚的代谢途径之一。近年来的研究表明,在该途径中除了查尔酮合成酶(chalcone synthase,CHS)、查尔酮异构酶(chalcone isomerase,CHI)和黄烷酮-3-羟化酶(flavanone-3-hydrolase,F3H)起着关键作用外,二氢黄酮醇-4-还原酶(dihydroflavonol 4-reductase,DFR)对花青素的合成也至关重要。DFR可催化3种二氢黄酮醇和2种黄烷酮生成5种不同的花青素前体,且DFR基因家族不同成员对各个底物的催化效率不同,因此它在一定程度上决定着植物中花青素的种类和含量,从而影响植物组织或器官的颜色。该文对近年来国内外有关DFR在花青素合成过程中的生物学功能与调控,包括DFR的特征、作用机制和系统进化以及环境、转录因子和一些结构基因与DFR的关系等方面的研究进展进行了综述,以期为DFR今后的研究和利用基因工程改变植物组织或器官的颜色提供理论依据。 相似文献
993.
Dof(DNA binding with one finger)蛋白是一类植物特异性转录因子,通常含有200~400个氨基酸和2个主要结构域。该家族成员的N 末端为高度保守的单锌指Dof结构域,具有与DNA和蛋白质相互作用的双重功能,其C末端的氨基酸序列则较为多变,是Dof蛋白重要的特异转录调控结构域。研究表明,Dof蛋白作为转录激活物或阻遏物参与了多方面的植物生长发育过程。随着基因组测序技术的发展,已有大量的Dof基因从植物基因组数据库中鉴定出来。该文对近年来国内外有关Dof基因家族的结构特点、全基因组鉴定、蛋白互作以及生物学功能等方面的研究进展进行综述,以期为Dof转录因子的深入研究提供参考。 相似文献
994.
为研究中国水仙类黄酮代谢调控网络,从中国水仙(Narcissus tazetta var.chinensis)中克隆得到一个R2R3-MYB基因,命名为NtMYB7(GenBank登录号:MF522208)。序列分析表明,NtMYB7基因cDNA开放阅读框(ORF)为753bp,编码250个氨基酸。氨基酸多重序列比对分析发现,NtMYB7含有R2和R3保守结构域,属于R2R3-MYB家族;系统进化树分析结果显示,NtMYB7与花青素合成抑制因子聚为一类。实时荧光定量PCR分析发现,NtMYB7基因在中国水仙不同时期花瓣和副冠以及不同器官中均有表达,且NtMYB7基因在鳞茎盘中表达量最高。瞬时表达分析发现,NtMYB7使花青素合成激活因子StMYB诱导产生的红色变浅;定量PCR分析表明,NtMYB7基因显著抑制烟草黄酮醇代谢分支FLS基因的表达,同时抑制StMYB激活的花青素和原花青素合成结构基因的表达。研究结果初步判断,NtMYB7基因是中国水仙类黄酮代谢途径的抑制因子。 相似文献
995.
漓江河岸带枫杨群落主要木本植物种群生态位 总被引:5,自引:0,他引:5
为了解漓江河岸带枫杨群落主要木本植物种群的生态位特征,在对其进行群落调查的基础上,利用Levins和Shannon生态位宽度、Schoener生态位相似性和Pianka生态位重叠指数对漓江河岸带枫杨群落乔木层、灌木层主要种群生态位进行定量分析.结果表明: 乔木层的枫杨、灌木层的石榕树和桑的生态位宽度较大;重要值较大的物种,其生态位宽度一般较大,但两者排名顺序并不完全一致.乔木层主要种群生态位相似性普遍小于灌木层,平均值分别为0.151和0.236,主要种群间的生态位相似性较小,各种群对资源利用的相似程度不高;乔木层主要种群生态位重叠普遍小于灌木层,它们的平均值分别为0.217和0.273,主要种群间的生态位重叠程度较低;生态位宽度与生态位相似性之间无显著相关关系,生态位宽度大的物种与其他物种发生重叠的概率更大,但生态位重叠值不一定大,生态位相似性大的物种,其生态位重叠值一般较大.漓江河岸带枫杨群落属于地带性顶极群落,种间关系相对稳定,种群更新缓慢,在发展中有衰退趋势. 相似文献
996.
Yuichiro Kawamoto Ryushi Seo Nobuhito Murai Hideki Hiyama Hiromasa Oka 《Bioorganic & medicinal chemistry》2018,26(1):257-265
Lysophosphatidic acid (LPA) plays an important role in a variety of cellular functions. In particular, LPA5 receptor is highly expressed in spinal cord and dorsal root ganglion, which are associated with pain. This fact prompted us to hypothesize that LPA5 antagonists show analgesic effects. To search for potent LPA5 antagonists with blood brain barrier (BBB) permeability, we conducted high throughput screening (HTS). In HTS campaign, we found a 2H-isoquinoline-1-one scaffold showing antagonistic activity against LPA5 and synthesized a series of 2H-isoquinoline-1-one derivatives and evaluated their LPA5 activities. Among these compounds, compound 7e showed potent LPA5 activity with an IC50 value of 0.12?μM, and acceptable BBB permeability. Furthermore, it showed effective analgesic effect in a chronic constriction injury rat model. Therefore, 7e may have a potential as novel pain therapeutic approach. 相似文献
997.
998.
999.
David D. Boehr Rebecca N. D'Amico Kathleen F. O'Rourke 《Protein science : a publication of the Protein Society》2018,27(4):825-838
Enzymes undergo a range of internal motions from local, active site fluctuations to large‐scale, global conformational changes. These motions are often important for enzyme function, including in ligand binding and dissociation and even preparing the active site for chemical catalysis. Protein engineering efforts have been directed towards manipulating enzyme structural dynamics and conformational changes, including targeting specific amino acid interactions and creation of chimeric enzymes with new regulatory functions. Post‐translational covalent modification can provide an additional level of enzyme control. These studies have not only provided insights into the functional role of protein motions, but they offer opportunities to create stimulus‐responsive enzymes. These enzymes can be engineered to respond to a number of external stimuli, including light, pH, and the presence of novel allosteric modulators. Altogether, the ability to engineer and control enzyme structural dynamics can provide new tools for biotechnology and medicine. 相似文献
1000.
《Protein science : a publication of the Protein Society》2018,27(8):1518-1525
The young investigator award from the Protein Society was a special honor for me because, at its essence, the goal of my laboratory is to define what obscure proteins do. Years ago, I stumbled into mitochondria as a venue for this work, and these organelles continue to define the biological theme of my laboratory. Our approaches are fairly broad, reflecting my own somewhat unorthodox training among diverse scientific fields spanning organic synthesis, chemical biology, mechanistic biochemistry, signal transduction, and systems biology. Yet, whatever the theme or the discipline, we aim to understand how proteins work—especially those that hide in the dark corners of mitochondria. Below, I recount my own path into this arena of protein science, and describe how my experiences along the way have shaped our current multi‐disciplinary efforts to define the inner workings of this complex biological system. 相似文献