全文获取类型
收费全文 | 8994篇 |
免费 | 637篇 |
国内免费 | 467篇 |
专业分类
10098篇 |
出版年
2024年 | 10篇 |
2023年 | 81篇 |
2022年 | 190篇 |
2021年 | 324篇 |
2020年 | 231篇 |
2019年 | 265篇 |
2018年 | 283篇 |
2017年 | 231篇 |
2016年 | 320篇 |
2015年 | 461篇 |
2014年 | 579篇 |
2013年 | 638篇 |
2012年 | 739篇 |
2011年 | 703篇 |
2010年 | 413篇 |
2009年 | 371篇 |
2008年 | 425篇 |
2007年 | 416篇 |
2006年 | 367篇 |
2005年 | 359篇 |
2004年 | 292篇 |
2003年 | 299篇 |
2002年 | 241篇 |
2001年 | 195篇 |
2000年 | 193篇 |
1999年 | 162篇 |
1998年 | 108篇 |
1997年 | 102篇 |
1996年 | 104篇 |
1995年 | 101篇 |
1994年 | 78篇 |
1993年 | 78篇 |
1992年 | 127篇 |
1991年 | 101篇 |
1990年 | 72篇 |
1989年 | 72篇 |
1988年 | 66篇 |
1987年 | 49篇 |
1986年 | 41篇 |
1985年 | 53篇 |
1984年 | 33篇 |
1983年 | 24篇 |
1982年 | 19篇 |
1981年 | 10篇 |
1979年 | 10篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1971年 | 7篇 |
1970年 | 7篇 |
1966年 | 7篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Nian Zhou Wayne Zeller Jun Zhang Emmanuel Onua Alex S. Kiselyov Jose Ramirez Guðrún Palsdottir Guðrún Halldorsdottir Þorkell Andrésson Mark E. Gurney Jasbir Singh 《Bioorganic & medicinal chemistry letters》2009,19(5):1528-1531
A series of potent and selective EP3 receptor antagonists are described. Utilizing a pharmacophore model developed for the EP3 receptor, a series of 3,4-disubstituted indoles were found to be efficient ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors. An optimized molecule 7c featured a sound profile and potency in the functional rat and human platelet aggregation assays. 相似文献
992.
993.
994.
Brian E. Roe Michael R. Tilley Howard H. Gu David Q. Beversdorf Wolfgang Sadee Timothy C. Haab Audrey C. Papp 《PloS one》2009,4(8)
With recent advances in understanding of the neuroscience of risk taking, attention is now turning to genetic factors that may contribute to individual heterogeneity in risk attitudes. In this paper we test for genetic associations with risk attitude measures derived from both the psychology and economics literature. To develop a long-term prospective study, we first evaluate both types of risk attitudes and find that the economic and psychological measures are poorly correlated, suggesting that different genetic factors may underlie human response to risk faced in different behavioral domains. We then examine polymorphisms in a spectrum of candidate genes that affect neurotransmitter systems influencing dopamine regulation or are thought to be associated with risk attitudes or impulsive disorders. Analysis of the genotyping data identified two single nucleotide polymorphisms (SNPs) in the gene encoding the alpha 4 nicotine receptor (CHRNA4, rs4603829 and rs4522666) that are significantly associated with harm avoidance, a risk attitude measurement drawn from the psychology literature. Novelty seeking, another risk attitude measure from the psychology literature, is associated with several COMT (catechol-O-methyl transferase) SNPs while economic risk attitude measures are associated with several VMAT2 (vesicular monoamine transporter) SNPs, but the significance of these associations did not withstand statistical adjustment for multiple testing and requires larger cohorts. These exploratory results provide a starting point for understanding the genetic basis of risk attitudes by considering the range of methods available for measuring risk attitudes and by searching beyond the traditional direct focus on dopamine and serotonin receptor and transporter genes. 相似文献
995.
996.
Yingnan Gu Changjiang Zhao Lin He Bowei Yan Jiejing Dong Zuotong Li Kejun Yang Jingyu Xu 《Journal of plant biochemistry and biotechnology.》2018,27(2):156-166
Diacylglycerol kinase (DGK) is a kind of phosphokinase that catalyzes the formation of signaling molecule phosphatidic acid. In this study, seven maize (Zea mays) DGK gene family members were identified by an exploration of maize genome via multiple online databases, and designated as ZmDGK1-7, respectively. The proteins encoded by ZmDGKs ranged from 487 to 716 amino acids, and had a molecular weight (MWs) between 54.6 and 80.2 kDa. Phylogenetic analysis revealed that ZmDGKs grouped into three clusters as described for known plant DGK families: Cluster I was composed of three maize DGKs, ZmDGK1, ZmDGK4 and ZmDGK5, cluster II contained ZmDGK6, and the isoforms ZmDGK2, ZmDGK3 and ZmDGK7 fell into cluster III. ZmDGK proteins featured the typical functional domains, while all seven ZmDGKs have a conserved catalytic domain DGKc, only the cluster I ZmDGKs have the DAG/PE binding domain. Most ZmDGK genes showed ubiquitous expression profiles at various developmental stages, while a high relative expression was observed at the tasseling stage. ZmDGK genes exhibited differential expression patterns in response to abiotic stresses including cold, salinity and drought, and all ZmDGK genes were found obviously up-regulated by cold. The distinct roles of ZmDGKs in cold response was also supported by the finding that an accumulation of DGK products–PA under low temperature. This study will help to better understand the roles of DGKs in the development and abiotic stress responses in major crops. 相似文献
997.
Jiping Fu Christopher Becker Li Cao Michael Capparelli Regis Denay Roger Fujimoto Yu Gai Zhaobo Gao Christian Guenat Subramanian Karur Hongyong Kim Weikuan Li Xiaolin Li Wei Li Thomas Lochmann Amy Lu Peichao Lu Alexandre Luneau Fabrice Gallou 《Bioorganic & medicinal chemistry》2018,26(4):957-969
Synthetic modification of cyclosporin A at P3-P4 positions led to the discovery of NIM258, a next generation cyclophilin inhibitor with excellent anti-hepatitis C virus potency, with decreased transporter inhibition, and pharmacokinetics suitable for coadministration with other drugs. Herein is disclosed the evolution of the synthetic strategy to from the original medicinal chemistry route, designed for late diversification, to a convergent and robust development synthesis. The chiral centers in the P4 fragment were constructed by an asymmetric chelated Claisen rearrangement in the presence of quinidine as the chiral ligand. Identification of advanced crystalline intermediates enabled practical supply of key intermediates. Finally, macrocyclization was carried out at 10% weight concentration by a general and unconventional “slow release” concept. 相似文献
998.
Die Ren Pan Ju Jianing Liu Dongsheng Ni Yuping Gu Yaoshui Long Qin Zhou Yajun Xie 《In vitro cellular & developmental biology. Animal》2018,54(2):111-119
Kidney mainly arises from the induction of metanephric mesenchymal cells (MM cells) and the ureteric bud (UB). Transmembrane protein-100 (Tmem100) consists of two transmembrane regions with strong temporal and spatial expression characteristics during renal development. However, the function of Tmem100 in mouse embryonic kidney-derived cells remained unclear. We provided qPCR to verify the relationship between Tmem100 and the BMP signal pathway. To clarify the role of Tmem100 in cell proliferation and apoptosis, we carry out EdU incorporation, annexin V- fluorescein isothiocyanate (FITC) apoptosis assay. Here, we find that the knockdown of Tmem100 increases the proliferation and apoptosis of mouse embryonic kidney-derived cells, and this promotion can be inhibited by knockdown of BMP7 at the same time; these results suggest that BMP7 plays a crucial role in Tmem100-regulated cell proliferation and apoptosis. qRT-PCR results further demonstrate that the deficiency of Tmem100 leads to BMP7 upregulation and overexpression could get opposite results. In BMP7-depleted MK3 cells, Tmem100 is highly upregulated and BMPR-II is downregulated. And in BMP7-overexpressed MK3 cells, the expression of Tmem100 is decreased. In BMPR-II-depleted MK3 cells, Tmem100 is downregulated and BMP7 expression remains still. These findings indicate that both BMP7 and BMPR-II can regulate Tmem100 and vice versa, and BMPR-II expression is regulated by BMP7. However, BMP7 has no association with BMPR-II in MK3 cells. Our data demonstrated the significant role of BMP7 in Tmem100-regulated cell proliferation and apoptosis and revealed the complicated regulation network among Tmem100, BMP7, and BMPR-II in mouse embryonic kidney-derived cells. 相似文献
999.
LncRNA-uc.40 silence promotes P19 embryonic cells differentiation to cardiomyocyte via the PBX1 gene
Rongqiang Wu Peng Xue Yu Wan Shizhong Wang Meng Gu 《In vitro cellular & developmental biology. Animal》2018,54(8):600-609
Uc.40 is a long noncoding RNA that is highly conserved among different species, although its function is unknown. It is highly expressed in abnormal human embryonic heart. We previously reported that overexpression of uc.40 promoted apoptosis and inhibited proliferation of P19 cells, and downregulated PBX1, which was identified as a potential target gene of uc.40. The current study evaluated the effects of uc40-siRNA-44 (siRNA against uc.40) on the differentiation, proliferation, apoptosis, and mitochondrial function in P19 cells, and investigated the relationship between uc.40 and PBX1 in cardiomyocytes. The uc.40 silencing expression was confirmed by quantitative real-time polymerase chain reaction (RT-PCR). Observation of morphological changes in transfected P19 cells during different stages of differentiation revealed that uc40-siRNA-44 increased the number of cardiomyocyes. There was no significant difference in the morphology or time of differentiation between the uc40-siRNA-44 group and the control group. uc40-siRNA-44 significantly promoted proliferation of P19 cells and inhibited serum starvation-induced apoptosis. There was no significant difference in mitochondrial DNA copy number or cellular ATP level between the two groups, and ROS levels were significantly decreased in uc40-siRNA-44-transfected cells. The levels of PBX1 and myocardial markers of differentiation were examined in transfected P19 cells; uc40-siRNA-44 downregulated myocardial markers and upregulated PBX1 expression. These results suggest that uc.40 may play an important role during the differentiation of P19 cells by regulation of PBX1 to promote proliferation and inhibit apoptosis. These studies provide a foundation for further study of uc.40/PBX1 in cardiac development. 相似文献
1000.
Tao Cong Jinping Gu Alex Pui-Wai Lee Zhijuan Shang Yinghui Sun Qiaobing Sun Hong Wei Na Chen Siyao Sun Tingting Fu 《Cardiovascular ultrasound》2018,16(1):13