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   148437篇
  免费   3008篇
  国内免费   497篇
化学   69821篇
晶体学   1154篇
力学   8551篇
综合类   2篇
数学   43299篇
物理学   29115篇
  2023年   509篇
  2022年   509篇
  2021年   928篇
  2020年   1081篇
  2019年   1055篇
  2018年   11715篇
  2017年   11198篇
  2016年   8164篇
  2015年   2813篇
  2014年   2394篇
  2013年   4730篇
  2012年   8389篇
  2011年   14828篇
  2010年   8323篇
  2009年   8340篇
  2008年   10529篇
  2007年   12594篇
  2006年   4096篇
  2005年   4914篇
  2004年   4691篇
  2003年   4523篇
  2002年   3240篇
  2001年   1704篇
  2000年   1590篇
  1999年   1104篇
  1998年   893篇
  1997年   810篇
  1996年   1019篇
  1995年   663篇
  1994年   723篇
  1993年   685篇
  1992年   664篇
  1991年   598篇
  1990年   581篇
  1989年   554篇
  1988年   475篇
  1987年   481篇
  1986年   443篇
  1985年   651篇
  1984年   620篇
  1983年   428篇
  1982年   543篇
  1981年   525篇
  1980年   490篇
  1979年   433篇
  1978年   429篇
  1977年   360篇
  1976年   400篇
  1975年   369篇
  1973年   357篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
52.
53.
In the present work we describe a two‐dimensional liquid chromatographic system (2D‐LC) with detection by mass spectrometry (MS) for the simultaneous separation of endogenous metabolites of clinical interest and excreted xenobiotics deriving from exposure to toxic compounds. The 2D‐LC system involves two orthogonal chromatographic modes, hydrophilic interaction liquid chromatography (HILIC) to separate polar endogenous metabolites and reversed‐phase (RP) chromatography to separate excreted xenobiotics of low and intermediate polarity. Additionally, the present proposal has the novelty of incorporating an on‐line sample treatment based on the use of restricted access materials (RAMs), which permits the direct injection of urine samples into the system. The work is focused on the instrumental coupling, studying all possible options and attempting to circumvent the problems of solvent incompatibility between the RAM device and the two chromatographic columns, HILIC and RP. The instrumental configuration developed, RAM‐HILIC‐RPLC‐MS/MS, allows the simultaneous assessment of urinary metabolites of clinical interest and excreted compounds derived from exposure to toxic agents with minimal sample manipulation. Thus, it may be of interest in areas such as occupational and environmental toxicology in order to explore the possible relationship between the two types of compounds. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
54.
Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.  相似文献   
55.
The gas‐phase ozonolysis of three methylated alkenes, i.e., trans‐2,2‐dimethyl‐3‐hexene (22dM3H), trans‐2,5‐dimethyl‐3‐hexene (25dM3H), and 4‐methyl‐1‐pentene (4M1P), has been investigated in the presence of sufficient hydroxyl radical scavenger in a laminar flow reactor at ambient temperature (296 ± 2 K) and P = 1 atm of dry air (RH ≤ 5%). Ozone levels in the reactor were monitored by an automatic analyzer. Alkene and gas‐phase product concentrations were determined via online sampling either on three‐bed adsorbent cartridges followed by thermodesorption and GC/FID‐MS analysis or on 2,4‐dinitrophenylhydrazine (DNPH) cartridges for subsequent HPLC/UV analysis. Reaction rate coefficients of (3.38 ± 0.12) × 10?17 for 22dM3H and (2.71 ± 0.26) × 10?17 for 25dM3H, both in cm3 molecule?1 s?1 units, have been obtained under pseudo–first‐order conditions. Primary carbonyl products have been identified for the three investigated alkenes, and branching ratios are reported. In the case of 4M1P ozonolysis, the yield of a Criegee intermediate was indirectly determined. Kinetics and product study results are compared to those of literature when available. This work represents the first investigation of reaction products in the ozonolysis of 22dM3H, 25dM3H, and 4M1P in a flow reactor.  相似文献   
56.
The development of a new three-component chromatography-free reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.  相似文献   
57.
58.
59.
60.
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