全文获取类型
收费全文 | 21480篇 |
免费 | 1743篇 |
国内免费 | 1785篇 |
出版年
2024年 | 33篇 |
2023年 | 274篇 |
2022年 | 665篇 |
2021年 | 1159篇 |
2020年 | 780篇 |
2019年 | 1008篇 |
2018年 | 929篇 |
2017年 | 634篇 |
2016年 | 938篇 |
2015年 | 1376篇 |
2014年 | 1549篇 |
2013年 | 1638篇 |
2012年 | 2006篇 |
2011年 | 1758篇 |
2010年 | 1031篇 |
2009年 | 948篇 |
2008年 | 1129篇 |
2007年 | 945篇 |
2006年 | 855篇 |
2005年 | 676篇 |
2004年 | 543篇 |
2003年 | 479篇 |
2002年 | 394篇 |
2001年 | 329篇 |
2000年 | 327篇 |
1999年 | 331篇 |
1998年 | 214篇 |
1997年 | 243篇 |
1996年 | 194篇 |
1995年 | 193篇 |
1994年 | 163篇 |
1993年 | 129篇 |
1992年 | 181篇 |
1991年 | 144篇 |
1990年 | 146篇 |
1989年 | 98篇 |
1988年 | 91篇 |
1987年 | 87篇 |
1986年 | 63篇 |
1985年 | 67篇 |
1984年 | 43篇 |
1983年 | 47篇 |
1982年 | 22篇 |
1981年 | 16篇 |
1980年 | 14篇 |
1979年 | 12篇 |
1978年 | 10篇 |
1969年 | 9篇 |
1968年 | 8篇 |
1965年 | 16篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
931.
932.
933.
934.
Ping Yu Wenjing Liu Jinghui Ren Yingying Wang Yao Ning Mingqi Huang Xinyi Hu Lili Wei Min Ji Jin Cai 《Bioorganic & medicinal chemistry letters》2019,29(16):2168-2172
Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipidemic compounds, and found that some of new analogues showed favorable hypolipidemic activities. Synthetic accessibility towards this class of compounds optimized RVX-208 as well as would supply more thoughts on hypolipidemic drugs. 相似文献
935.
936.
Ling-Pan Lu Jin-Hai Liu Shi-Hong Cen Ya-Ling Jiang Guo-Qiang Hu 《Bioorganic & medicinal chemistry letters》2019,29(4):681-683
Lysine specific demethylase (LSD1) plays a pivotal role in epigenetic modulation of gene expression. Abberrant expression of LSD1 was associated with the progress and oncogenesis of multiple human cancers. Herein, we report the preliminary anti-LSD1 evaluation of the synthetic vanadium (V) complexes. Among them, complex 2 showed a moderate inhibitory effect against LSD1 with IC50 value of 19.0?μM, as well as good selectivity over MAO-A/B. Complex 2 is the first vanadium based LSD1 inhibitor, which provides a novel scaffold for the development of LSD1 inhibitor. 相似文献
937.
938.
Kai Wang Hanjing Hu Huizhen Yan Dandi Hou Yanting Wang Pengsheng Dong Demin Zhang 《Molecular ecology》2019,28(12):3101-3118
Marine Archaea are crucial in biogeochemical cycles, but their horizontal spatial variability, assembly processes, and microbial associations across complex coastal waters still lack characterizations at high coverage. Using a dense sampling strategy, we investigated horizontal variability in total archaeal, Thaumarchaeota Marine Group (MG) I, and Euryarchaeota MGII communities and associations of MGI/MGII with other microbes in surface waters with contrasting environmental characteristics across ~200 km by 16S rRNA gene amplicon sequencing. Total archaeal communities were extremely dominated by MGI and/or MGII (98.9% in average relative abundance). Niche partitioning between MGI and MGII or within each group was found across multiple environmental gradients. “Selection” was more important than “dispersal limitation” in governing biogeographic patterns of total archaeal, MGI, and MGII communities, and basic abiotic parameters (such as salinity) and inorganic/organic resources as a whole could be the main driver of “selection”. While “homogenizing dispersal” also considerably governed their biogeography. MGI‐Nitrospira assemblages were speculatively responsible for complete nitrification. MGI taxa commonly had negative correlations with members of Synechococcus but positive correlations with members of eukaryotic phytoplankton, suggesting that competition or synergy between MGI and phytoplankton depends on specific MGI‐phytoplankton assemblages. MGII taxa showed common associations with presumed (photo)heterotrophs including members of SAR11, SAR86, SAR406, and Candidatus Actinomarina. This study sheds light on ecological processes and drivers shaping archaeal biogeography and many strong MGI/MGII‐bacterial associations across complex subtropical coastal waters. Future efforts should be made on seasonality of archaeal biogeography and biological, environmental, or ecological mechanisms underlying these statistical microbial associations. 相似文献
939.
Shyh-Ming Yang Makoto Yoshioka Jeffrey W. Strovel Daniel J. Urban Xin Hu Matthew D. Hall Ajit Jadhav David J. Maloney 《Bioorganic & medicinal chemistry letters》2019,29(10):1220-1226
Extensive optimization of quinazoline-based lead 8 is described. The structure-activity relationship studies indicate the S-configuration is preferred for the phenylmorpholine substitution. Together with incorporation of a (2-hydroxyl-2-methylpropyl)pyrazole moiety at the 2-position leads to analogs with comparable potency and marked improvement in the pharmacokinetic profile over our previously reported lead compounds. Further in vivo efficacy studies in Kasumi-1 xenograft mouse model demonstrates that the selected inhibitors are well tolerated and highly efficacious in the inhibition of tumor growth. Additionally, the representative analog 19 also demonstrated significant improvement of arthritis severity in a collagen-induced arthritis (CIA) mouse model. These results indicate potential use of these quinazoline-based BET inhibitors for treatment of cancer and inflammatory diseases. A brief discussion of the co-crystallized structure of 19 with BRD4 (BD1) is also highlighted. 相似文献
940.
Fan Wu Chuan Ma Bin Han Lifeng Meng Han Hu Yu Fang Mao Feng Xufeng Zhang Olav Rueppell Jianke Li 《Molecular ecology》2019,28(18):4212-4227
Reproductive investment is a central life history variable that influences all aspects of life. Hormones coordinate reproduction in multicellular organisms, but the mechanisms controlling the collective reproductive investment of social insects are largely unexplored. One important aspect of honey bee (Apis mellifera) reproductive investment consists of raising female‐destined larvae into new queens by alloparental care of nurse bees in form of royal jelly provisioning. Artificial selection for commercial royal jelly production over 40 years has increased this reproductive investment by an order of magnitude. In a cross‐fostering experiment, we establish that this shift in social phenotype is caused by nurse bees. We find no evidence for changes in larval signalling. Instead, the antennae of the nurse bees of the selected stock are more responsive to brood pheromones than control bees. Correspondingly, the selected royal jelly bee nurses are more attracted to brood pheromones than unselected control nurses. Comparative proteomics of the antennae from the selected and unselected stocks indicate putative molecular mechanisms, primarily changes in chemosensation and energy metabolism. We report expression differences of several candidate genes that correlate with the differences in reproductive investment. The functional relevance of these genes is supported by demonstrating that the corresponding proteins can competitively bind one previously described and one newly discovered brood pheromone. Thus, we suggest several chemosensory genes, most prominently OBP16 and CSP4, as candidate mechanisms controlling queen rearing, a key reproductive investment, in honey bees. These findings reveal novel aspects of pheromonal communication in honey bees and explain how sensory changes affect communication and lead to a drastic shift in colony‐level resource allocation to sexual reproduction. Thus, pheromonal and hormonal communication may play similar roles for reproductive investment in superorganisms and multicellular organisms, respectively. 相似文献