全文获取类型
收费全文 | 43754篇 |
免费 | 3954篇 |
国内免费 | 19篇 |
出版年
2023年 | 129篇 |
2022年 | 396篇 |
2021年 | 783篇 |
2020年 | 448篇 |
2019年 | 595篇 |
2018年 | 730篇 |
2017年 | 641篇 |
2016年 | 1155篇 |
2015年 | 1953篇 |
2014年 | 2081篇 |
2013年 | 2512篇 |
2012年 | 3336篇 |
2011年 | 3450篇 |
2010年 | 2146篇 |
2009年 | 1994篇 |
2008年 | 2801篇 |
2007年 | 2835篇 |
2006年 | 2669篇 |
2005年 | 2500篇 |
2004年 | 2426篇 |
2003年 | 2241篇 |
2002年 | 2135篇 |
2001年 | 573篇 |
2000年 | 427篇 |
1999年 | 537篇 |
1998年 | 559篇 |
1997年 | 411篇 |
1996年 | 365篇 |
1995年 | 337篇 |
1994年 | 297篇 |
1993年 | 325篇 |
1992年 | 353篇 |
1991年 | 275篇 |
1990年 | 266篇 |
1989年 | 261篇 |
1988年 | 230篇 |
1987年 | 204篇 |
1986年 | 161篇 |
1985年 | 208篇 |
1984年 | 222篇 |
1983年 | 172篇 |
1982年 | 171篇 |
1981年 | 147篇 |
1980年 | 128篇 |
1979年 | 110篇 |
1978年 | 120篇 |
1977年 | 112篇 |
1976年 | 88篇 |
1974年 | 71篇 |
1973年 | 77篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels
Kelly L. McGuire Phillip Smit Daniel H. Ess Jonathan T. Hill Roger G. Harrison David D. Busath 《Biophysical journal》2021,120(1):168-177
Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block showed fast and slow phases, in contrast to the single phase found for amantadine block of wild-type M2. Here, we evaluate the mechanism of block by copper adamantyl iminodiacitate and copper cyclooctyl iminodiacitate complexes and address whether the complexes can coordinate with one or more of the His37 imidazoles. The current traces were fitted to parametrized master equations. The energetics of binding and the rate constants suggest that the first step is copper complex binding within the channel, and the slow step in the current block is the formation of a Cu-histidine coordination complex. Solution-phase isothermal titration calorimetry and density functional theory (DFT) calculations indicate that imidazole binds to the copper complexes. Structural optimization using DFT reveals that the complexes fit inside the channel and project the Cu(II) toward the His37 cluster, allowing one imidazole to form a coordination complex with Cu(II). Electrophysiology and DFT studies also show that the complexes block the G34E amantadine-resistant mutant despite some crowding in the binding site by the glutamates. 相似文献
952.
953.
954.
955.
956.
Hui Li Shuyi Wang Fang-Hua Lee Ryan S. Roark Alex I. Murphy Jessica Smith Chengyan Zhao Juliette Rando Neha Chohan Yu Ding Eunlim Kim Emily Lindemuth Katharine J. Bar Ivona Pandrea Cristian Apetrei Brandon F. Keele Jeffrey D. Lifson Mark G. Lewis Thomas N. Denny Barton F. Haynes Beatrice H. Hahn George M. Shaw 《Journal of virology》2021,95(11)
957.
Maren de Vries Adil S. Mohamed Rachel A. Prescott Ana M. Valero-Jimenez Ludovic Desvignes Rebecca OConnor Claire Steppan Joseph C. Devlin Ellie Ivanova Alberto Herrera Austin Schinlever Paige Loose Kelly Ruggles Sergei B. Koralov Annaliesa S. Anderson Joseph Binder Meike Dittmann 《Journal of virology》2021,95(10)
958.
959.
960.
Malachy T Campbell Haixiao Hu Trevor H Yeats Melanie Caffe-Treml Lucía Gutirrez Kevin P Smith Mark E Sorrells Michael A Gore Jean-Luc Jannink 《Genetics》2021,217(3)
Oat (Avena sativa L.) seed is a rich resource of beneficial lipids, soluble fiber, protein, and antioxidants, and is considered a healthful food for humans. Little is known regarding the genetic controllers of variation for these compounds in oat seed. We characterized natural variation in the mature seed metabolome using untargeted metabolomics on 367 diverse lines and leveraged this information to improve prediction for seed quality traits. We used a latent factor approach to define unobserved variables that may drive covariance among metabolites. One hundred latent factors were identified, of which 21% were enriched for compounds associated with lipid metabolism. Through a combination of whole-genome regression and association mapping, we show that latent factors that generate covariance for many metabolites tend to have a complex genetic architecture. Nonetheless, we recovered significant associations for 23% of the latent factors. These associations were used to inform a multi-kernel genomic prediction model, which was used to predict seed lipid and protein traits in two independent studies. Predictions for 8 of the 12 traits were significantly improved compared to genomic best linear unbiased prediction when this prediction model was informed using associations from lipid-enriched factors. This study provides new insights into variation in the oat seed metabolome and provides genomic resources for breeders to improve selection for health-promoting seed quality traits. More broadly, we outline an approach to distill high-dimensional “omics” data to a set of biologically meaningful variables and translate inferences on these data into improved breeding decisions. 相似文献