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   1596篇
  免费   60篇
  国内免费   515篇
  2024年   1篇
  2023年   27篇
  2022年   29篇
  2021年   49篇
  2020年   58篇
  2019年   60篇
  2018年   38篇
  2017年   51篇
  2016年   68篇
  2015年   82篇
  2014年   135篇
  2013年   135篇
  2012年   148篇
  2011年   180篇
  2010年   117篇
  2009年   142篇
  2008年   154篇
  2007年   158篇
  2006年   136篇
  2005年   68篇
  2004年   59篇
  2003年   32篇
  2002年   27篇
  2001年   19篇
  2000年   14篇
  1999年   11篇
  1998年   13篇
  1997年   14篇
  1996年   17篇
  1995年   13篇
  1994年   19篇
  1993年   16篇
  1992年   12篇
  1991年   14篇
  1990年   7篇
  1989年   3篇
  1988年   9篇
  1987年   14篇
  1986年   15篇
  1985年   2篇
  1983年   2篇
  1958年   1篇
  1950年   2篇
排序方式: 共有2171条查询结果,搜索用时 15 毫秒
191.
《Inorganica chimica acta》2006,359(4):1050-1054
A novel series of inorganic–organic intercalation compounds were prepared by intercalating of alkylviologen dications into the layered vanadium pentoxide in the system of two phases of the liquid and the solid, and characterized by the techniques of X-ray diffraction (XRD), FT infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and UV/vis diffuse reflectance spectroscopy (DRS).  相似文献   
192.
《Developmental cell》2023,58(5):361-375.e5
  1. Download : Download high-res image (169KB)
  2. Download : Download full-size image
  相似文献   
193.
194.
A 96-member chelator fragment library (CFL-1.1) was screened to identify inhibitors of the lymphoid tyrosine phosphatase in the absence and presence of zinc acetate. Fragments that inhibit LYP activity more potently in the presence of zinc, fragments that rescue LYP activity in the presence of inhibitory concentrations of zinc, and fragments that inhibit LYP activity independent of zinc concentration were identified. Of these, 1,2-dihydroxynaphthalene was the most potent inhibitor with an IC50 value of 2.52 ± 0.06 μM after 2 h of incubation. LYP inhibition by 1,2-dihydroxynaphthalene was very similar to inhibition by 1,2-naphthoquinone (IC50 = 1.10 ± 0.03 µM), indicating that the oxidized quinone species is likely the active inhibitor. The inhibition was time-dependent, consistent with covalent modification of the enzyme.  相似文献   
195.
PTP1B (protein tyrosine phosphatase 1B) dephosphorylates the insulin receptor substrate and thus acts as a negative regulator of the insulin and leptin signalling pathway. Recently, it has been considered as a new therapeutic target of intervention for the treatment of type2 diabetes. A series of aryl/alkylsulfonyloxy-5-(3-methoxybenzylidene)thiazolidine-2,4-dione derivatives were synthesized, screened in vitro for their PTP1B inhibitory activity and in vivo for anti-hyperglycaemic activity. Docking results further helped in understanding the nature of interactions governing the binding mode of ligands inside the active site of PTP1B. Among the synthesized compounds, 13 and 16 were found to be potent PTP1B inhibitors having IC50 of 7.31 and 8.73 μM respectively. Significant lowering of blood glucose level was observed in some of the synthesized compounds in in vivo study.  相似文献   
196.
An efficient one-pot three enzymes strategy for chemoenzymatic synthesis of ADP-d-glycero-β-d-manno-heptose (ADP-d, d-heptose) was reported using chemically synthesized d, d-heptose-7-phosphate and the ADP-d, d-heptose biosynthetic enzymes HldE and GmhB. Moreover, the result of investigating substrate specificity of the kinase action of HldE revealed that HldE had highly restricted substrate specificity towards structurally modified heptose-7-phosphate analogs.  相似文献   
197.
《Phytomedicine》2014,21(3):323-332
The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibited some level of cytotoxicity against both CCRF-CEM and CEM/ADR5000 cells. In ATPase assays, three of the four guanidine alkaloids were found to stimulate the ATPase activity of ABCB1. Notably, nitensidine A was clearly found to stimulate the ATPase activity of ABCB1 as strongly as the control drug, verapamil. Furthermore, the cytotoxic effect of nitensidine A on CEM/ADR5000 cells was synergistically enhanced by verapamil. Nitensidine A inhibited the extrusion of calcein by ABCB1. In the present study, the possibility of interaction between ABCB1 and two synthetic nitensidine A analogs (nitensidine AT and AU) were examined to gain insight into the mechanism by which nitensidine A stimulates the ATPase activity of ABCB1. The ABCB1-dependent ATPase activity stimulated by nitensidine A was greatly reduced by substituting sulfur (S) or oxygen (O) for the imino nitrogen atom (N) in nitensidine A. Molecular docking studies on human ABCB1 showed that, guanidine alkaloids from P. nitens dock to the same binding pocket as verapamil. Nitensidine A and its analogs exhibit similar binding energies to verapamil. Taken together, this research clearly indicates that nitensidine A is a novel substrate for ABCB1. The present results also suggest that the number, binding site, and polymerization degree of the isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their stimulation of ABCB1's ATPase activity.  相似文献   
198.
Evidence shows that an abnormal deposition of amyloid beta-peptide25–35 (Aβ25–35) was the primary cause of the pathogenesis of Alzheimer’s disease (AD). And the elimination of Aβ25–35 is considered an important target for the treatment of AD. Triptolide (TP), isolated from Tripterygium wilfordii Hook.f. (TWHF), has been shown to possess a broad spectrum of biological profiles, including neurotrophic and neuroprotective effects. In our study investigating the effect and potential mechanism of triptolide on cytotoxicity of differentiated rat pheochromocytoma cell line (the PC12 cell line is often used as a neuronal developmental model) induced by Amyloid-Beta25–35 (Aβ25–35), we used 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT) assay, flow cytometry, Western blot, and acridine orange staining to detect whether triptolide could inhibit Aβ25–35–induced cell apoptosis. We focused on the potential role of the autophagy pathway in Aβ25–35-treated differentiated PC12 cells. Our experiments show that cell viability is significantly decreased, and the apoptosis increased in Aβ25–35-treated differentiated PC12 cells. Meanwhile, Aβ25–35 treatment increased the expression of microtubule-associated protein light chain 3 II (LC3 II), which indicates an activation of autophagy. However, triptolide could protect differentiated PC12 cells against Aβ25–35-induced cytotoxicity and attenuate Aβ25–35-induced differentiated PC12 cell apoptosis. Triptolide could also suppress the level of autophagy. In order to assess the effect of autophagy on the protective effects of triptolide in differentiated PC12 cells treated with Aβ25–35, we used 3-Methyladenine (3-MA, an autophagy inhibitor) and rapamycin (an autophagy activator). MTT assay showed that 3-MA elevated cell viability compared with the Aβ25–35-treated group and rapamycin inhibits the protection of triptolide. These results suggest that triptolide will repair the neurological damage in AD caused by deposition of Aβ25–35 via the autophagy pathway, all of which may provide an exciting view of the potential application of triptolide or TWHF as a future research for AD.  相似文献   
199.
Rapid urbanization has exerted substantial pressure on China’s energy system and contributed to climate change. To find the key drivers of urban residential energy consumption and CO2 emissions, this paper uses an extended Stochastic Impacts by Regression on Population, Affluence and Technology (STIRPAT) model that employs city-level data to examine the influences of population scale, income level, population compactness and price on house-based residential energy consumption, energy-related CO2 emissions and private vehicle ownership. The empirical results indicate that factors such as population scale, affluence, and population compactness can lead to increases in residential energy consumption and CO2 emissions. In terms of transportation, income and population scale positively drive the growth of private vehicle ownership, while the fuel price negatively influences private vehicle ownership. Moreover, population scale is the most important factor in residential energy consumption and CO2 emissions. Finally, policy recommendations are suggested for China’s urban development strategy and urban design and to encourage technology innovations that reduce residential energy consumption and CO2 emissions.  相似文献   
200.
He  Ziying  Peng  Yisheng  Guan  Dongsheng  Hu  Zhan  Chen  Yujuan  Lee  Shing Yip 《Plant and Soil》2018,429(1-2):425-436
Plant and Soil - A dominant species of steppe in northern China, Stipa grandis, is gradually being replaced by S. krylovii due to climate change events. The aim of this study was...  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