全文获取类型
收费全文 | 20746篇 |
免费 | 2311篇 |
国内免费 | 1064篇 |
出版年
2023年 | 137篇 |
2022年 | 305篇 |
2021年 | 516篇 |
2020年 | 428篇 |
2019年 | 494篇 |
2018年 | 560篇 |
2017年 | 480篇 |
2016年 | 675篇 |
2015年 | 947篇 |
2014年 | 1124篇 |
2013年 | 1168篇 |
2012年 | 1412篇 |
2011年 | 1391篇 |
2010年 | 880篇 |
2009年 | 817篇 |
2008年 | 1051篇 |
2007年 | 969篇 |
2006年 | 829篇 |
2005年 | 763篇 |
2004年 | 725篇 |
2003年 | 602篇 |
2002年 | 567篇 |
2001年 | 1309篇 |
2000年 | 1111篇 |
1999年 | 816篇 |
1998年 | 296篇 |
1997年 | 287篇 |
1996年 | 215篇 |
1995年 | 182篇 |
1994年 | 183篇 |
1993年 | 122篇 |
1992年 | 388篇 |
1991年 | 343篇 |
1990年 | 297篇 |
1989年 | 234篇 |
1988年 | 213篇 |
1987年 | 147篇 |
1986年 | 153篇 |
1985年 | 116篇 |
1984年 | 67篇 |
1983年 | 71篇 |
1981年 | 33篇 |
1979年 | 43篇 |
1978年 | 34篇 |
1976年 | 38篇 |
1975年 | 35篇 |
1973年 | 39篇 |
1972年 | 50篇 |
1971年 | 45篇 |
1970年 | 35篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
901.
902.
Mckayla Stevens Sanofar Abdeen Nilshad Salim Anne-Marie Ray Alex Washburn Siddhi Chitre Jared Sivinski Yangshin Park Quyen Q. Hoang Eli Chapman Steven M. Johnson 《Bioorganic & medicinal chemistry letters》2019,29(9):1106-1112
All living organisms contain a unique class of molecular chaperones called 60?kDa heat shock proteins (HSP60 – also known as GroEL in bacteria). While some organisms contain more than one HSP60 or GroEL isoform, at least one isoform has always proven to be essential. Because of this, we have been investigating targeting HSP60 and GroEL chaperonin systems as an antibiotic strategy. Our initial studies focused on applying this antibiotic strategy for treating African sleeping sickness (caused by Trypanosoma brucei parasites) and drug-resistant bacterial infections (in particular Methicillin-resistant Staphylococcus aureus – MRSA). Intriguingly, during our studies we found that three known antibiotics – suramin, closantel, and rafoxanide – were potent inhibitors of bacterial GroEL and human HSP60 chaperonin systems. These findings prompted us to explore what other approved drugs, natural products, and known bioactive molecules might also inhibit HSP60 and GroEL chaperonin systems. Initial high-throughput screening of 3680 approved drugs, natural products, and known bioactives identified 161 hit inhibitors of the Escherichia coli GroEL chaperonin system (4.3% hit rate). From a purchased subset of 60 hits, 29 compounds (48%) re-confirmed as selective GroEL inhibitors in our assays, all of which were nearly equipotent against human HSP60. These findings illuminate the notion that targeting chaperonin systems might be a more common occurrence than we previously appreciated. Future studies are needed to determine if the in vivo modes of action of these approved drugs, natural products, and known bioactive molecules are related to GroEL and HSP60 inhibition. 相似文献
903.
Jeyun Jo Heegyu Kim Ji Youn Oh Soyeong Kim Yeong Hye Park Hyeonjin Choi Jee-Yeong Jeong Young-Suk Jung Hwayoung Yun 《Bioorganic & medicinal chemistry letters》2019,29(24):126752
Triple-negative breast cancers (TNBCs) account for approximately 15% of breast cancer cases and exhibit an aggressive clinical behavior. In this study, we designed and synthesized two series of 2-anilinopyrimidines based on the structure of our previously reported compound 1 that act as a selective inhibitor of the basal-like TNBC cell line MDA-MB-468. Through the fine-tuning of 1, cyclic and acyclic amines at 4-position of the pyrimidine core were turned out to be crucial for the selectivity. An extensive analysis of structure-activity relationships of the analogs revealed that aminoalkyl groups at the end of the propyl chain are amenable to modification. Among the newly synthesized analogs, compound 38, bearing 4-chloropiperidinyl and cyclohexyl groups, was found to be the most potent and selective, and was about three times more potent and selective than 1 was against the TNBC cells. 相似文献
904.
905.
906.
Susana Q. Lima 《Current biology : CB》2019,29(21):R1122-R1124
907.
Yun Ren Dan Chen Wenjie Li Dan Zhou Tao Luo Guoqiang Yuan Jing Zeng Ye Cao Zhongshan He Ting Zou Qiming Deng Shiquan Wang Aiping Zheng Jun Zhu Yueyang Liang Huainian Liu Lingxia Wang Ping Li Shuangcheng Li 《The Plant journal : for cell and molecular biology》2019,98(2):315-328
Meiosis is essential for eukaryotic sexual reproduction and plant fertility, and crossovers (COs) are essential for meiosis and the formation of new allelic combinations in gametes. In this study, we report the isolation of a meiotic gene, OsSHOC1, and the identification of its partner, OsPTD1. Osshoc1 was sterile both in male and female gametophytes, and it showed a striking reduction in the number of meiotic COs, indicating that OsSHOC1 was required for normal CO formation. Further investigations showed that OsSHOC1 physically interacted with OsPTD1 and that the latter was also required for normal CO formation and plant fertility. Additionally, the expression profiles of both genes were consistent with their functions. Our results suggest that OsSHOC1 and OsPTD1 are essential for rice fertility and CO formation, possibly by stabilizing the recombinant intermediates during meiosis. 相似文献
908.
909.
910.
Gregory B. Noe Meghan Q.N. Fellows Lorraine Parsons Janelle West John Callaway Sally Trnka Mark Wegener Joy Zedler 《Restoration Ecology》2019,27(4):750-757
In theory, extirpated plant species can be reintroduced and managed to restore sustainable populations. However, few reintroduced plants are known to persist for more than a few years. Our adaptive‐management case study illustrates how we restored the endangered hemiparasitic annual plant, Chloropyron maritimum subsp. maritimum (salt marsh bird's beak), to Sweetwater Marsh, San Diego Bay National Wildlife Refuge, California, United States, and used monitoring and experimentation to identify the factors limiting the reintroduced population. After extirpation in 1988, reintroduction starting that year led to a resilient, genetically diverse population in 2016 (a “boom” of approximately 14,000) that rebounded from a “bust” (62 in 2014). Multiple regressions attributed 82% of the variation in population counts to tidal amplitude, rainfall, and temperature. Populations of salt marsh bird's beak crashed when the diurnal tide range peaked during the 18.6‐year lunar nodal cycle (a rarely considered factor that periodically added approximately 12 cm to tidal ranges). We explain booms as follows: During smaller tidal amplitudes, above‐average rainfall could desalinize upper intertidal soils and stimulate salt marsh bird's beak germination. Then, moderate temperature in May favors growth to reproduction in June. In addition, salt marsh bird's beak needs a short and open canopy of native perennial plants, with roots to parasitize (not non‐native annual grass pseudohosts) and nearby upland soil for a preferred pollinator, ground‐burrowing bees. Although our reintroduced salt marsh bird's beak population is an exceptional case of persistence, this rare species‐specific environmental and biological requirement makes it vulnerable to rising sea levels and global warming. 相似文献