首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   87905篇
  免费   6061篇
  国内免费   3291篇
  2023年   1346篇
  2022年   1418篇
  2021年   2844篇
  2020年   2825篇
  2019年   3890篇
  2018年   3421篇
  2017年   2458篇
  2016年   2454篇
  2015年   3010篇
  2014年   5614篇
  2013年   7123篇
  2012年   4362篇
  2011年   5620篇
  2010年   4295篇
  2009年   4645篇
  2008年   4713篇
  2007年   4747篇
  2006年   4229篇
  2005年   3671篇
  2004年   3247篇
  2003年   2627篇
  2002年   2340篇
  2001年   1515篇
  2000年   1218篇
  1999年   1222篇
  1998年   1201篇
  1997年   955篇
  1996年   870篇
  1995年   795篇
  1994年   727篇
  1993年   593篇
  1992年   568篇
  1991年   490篇
  1990年   404篇
  1989年   335篇
  1988年   294篇
  1987年   261篇
  1986年   246篇
  1985年   405篇
  1984年   664篇
  1983年   517篇
  1982年   542篇
  1981年   433篇
  1980年   347篇
  1979年   315篇
  1978年   271篇
  1977年   247篇
  1976年   207篇
  1975年   188篇
  1973年   178篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
61.
This review is focused on the different chromatographic strategies for determination of finasteride and its analogues in biological fluids. These compounds are used for the treatment of benign prostatic hyperplasia. Particular attention is paid to high-performance liquid chromatography with spectrophotometric and mass spectrometric detection, the clean-up procedures are also included. The relationships between pharmacokinetics of finasteride, dose administered and required limit of quantitation of the chromatographic assays are discussed. Tandem mass spectrometry is recommended as the detection method for measuring concentrations <1 ng/ml, while cheaper spectrophotometric detection may be selected for determination of higher concentrations.  相似文献   
62.
RegB is involved in the control of the phage T4 life cycle. It inactivates the phage early mRNAs when their translation is no more required. We determined its structure and identified residues involved in substrate binding. For this, all backbone and 90% of side-chain resonance frequencies were assigned.  相似文献   
63.
皮肤作为人体最大器官覆盖于全身,能阻挡有害物质的侵入,保护人体内环境稳态,参与人体代谢过程。皮肤损伤、炎症和纤维化等,都会导致皮肤屏障功能的减退,影响正常的生命活动。溶血磷脂酸(lysophosphatidic acid,LPA)是十分活跃的磷脂信号分子,参与多种生理和病理生理过程。LPA是维持体内平衡所必需的生物活性脂质介质,在皮肤中通过不同的信号通路发挥多功能磷脂信使作用。本文综述了皮肤中溶血磷脂酸受体(lysophosphatidic acid receptor,LPA1-6)及其细胞信号通路的作用及机制,综述了LPA在皮肤创面愈合、皮肤瘢痕、皮肤黑色素瘤、硬皮病、皮肤瘙痒、过敏性皮炎、皮肤屏障、皮肤疼痛,皮肤毛发生长中的作用及分子机制,有助于了解LPA在皮肤中的生理和病理生理作用。深入研究LPA的作用机制将有助于挖掘其在皮肤治疗中的作用,开发以LPA为靶点的药物。  相似文献   
64.
The antiretroviral activity of azulene derivatives was detected for the first time. A series of eighteen diversely substituted azulenes was synthesized and tested in vitro using HIV-1 based virus-like particles (VLPs) and infectious HIV-1 virus in U2OS and TZM-bl cell lines. Among the compounds tested, the 2-hydroxyazulenes demonstrated the most significant activity by inhibiting HIV-1 replication with IC50 of 2–10 and 8–20 μM for the VLPs and the infectious virus, respectively. These results indicate that azulene derivatives may be potentially useful candidates for the development of antiretroviral agents.  相似文献   
65.
66.
In Saccharomyces cerevisiae, the unconventional myosin Myo2p is of fundamental importance in polarized growth. We explore the role of the neck region and its associated light chains in regulating Myo2p function. Surprisingly, we find that precise deletion of the six IQ sites in the neck region results in a myosin, Myo2-Δ6IQp, that can support the growth of a yeast strain at 90% the rate of a wild-type isogenic strain. We exploit this mutant in a characterization of the light chains of Myo2p. First, we demonstrate that the localization of calmodulin to sites of polarized growth largely depends on the IQ sites in the neck of Myo2p. Second, we demonstrate that a previously uncharacterized protein, Mlc1p, is a myosin light chain of Myo2p. MLC1 (YGL106w) is an essential gene that exhibits haploinsufficiency. Reduced levels of MYO2 overcome the haploinsufficiency of MLC1. The mutant MYO2-Δ6IQ is able to suppress haploinsufficiency but not deletion of MLC1. We used a modified gel overlay assay to demonstrate a direct interaction between Mlc1p and the neck of Myo2p. Overexpression of MYO2 is toxic, causing a severe decrease in growth rate. When MYO2 is overexpressed, Myo2p is fourfold less stable than in a wild-type strain. High copies of MLC1 completely overcome the growth defects and increase the stability of Myo2p. Our results suggest that Mlc1p is responsible for stabilizing this myosin by binding to the neck region.  相似文献   
67.
Aims/hypothesisGlucagon-like peptide-1 (GLP-1) is an incretin hormone derived from proglucagon, which is released from intestinal L-cells and increases insulin secretion in a glucose dependent manner. GPR119 is a lipid derivative receptor present in L-cells, believed to play a role in the detection of dietary fat. This study aimed to characterize the responses of primary murine L-cells to GPR119 agonism and assess the importance of GPR119 for the detection of ingested lipid.MethodsGLP-1 secretion was measured from murine primary cell cultures stimulated with a panel of GPR119 ligands. Plasma GLP-1 levels were measured in mice lacking GPR119 in proglucagon-expressing cells and controls after lipid gavage. Intracellular cAMP responses to GPR119 agonists were measured in single primary L-cells using transgenic mice expressing a cAMP FRET sensor driven by the proglucagon promoter.ResultsL-cell specific knockout of GPR119 dramatically decreased plasma GLP-1 levels after a lipid gavage. GPR119 ligands triggered GLP-1 secretion in a GPR119 dependent manner in primary epithelial cultures from the colon, but were less effective in the upper small intestine. GPR119 agonists elevated cAMP in ∼70% of colonic L-cells and 50% of small intestinal L-cells.Conclusions/interpretationGPR119 ligands strongly enhanced GLP-1 release from colonic cultures, reflecting the high proportion of colonic L-cells that exhibited cAMP responses to GPR119 agonists. Less GPR119-dependence could be demonstrated in the upper small intestine. In vivo, GPR119 in L-cells plays a key role in oral lipid-triggered GLP-1 secretion.  相似文献   
68.
Copper is an essential yet toxic metal ion. To satisfy cellular requirements, while, at the same time, minimizing toxicity, complex systems of copper trafficking have evolved in all cell types. The best conserved and most widely distributed of these involve Atx1-like chaperones and P1B-type ATPase transporters. Here, we discuss current understanding of how these chaperones bind Cu(I) and transfer it to the Atx1-like N-terminal domains of their cognate transporter.  相似文献   
69.
70.
Amino derivatives of NCI8642 were synthesized and evaluated as inhibitors of DKK1/LRP6 interactions. The new inhibitors were able to activate the Wnt signaling pathway as indicated by the increased levels of β-catenin, and decrease the DKK1-induced Tau phosphorylation at serine 396.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号