全文获取类型
收费全文 | 203711篇 |
免费 | 2658篇 |
国内免费 | 651篇 |
专业分类
化学 | 114479篇 |
晶体学 | 3324篇 |
力学 | 7968篇 |
综合类 | 4篇 |
数学 | 19808篇 |
物理学 | 61437篇 |
出版年
2016年 | 2651篇 |
2015年 | 2031篇 |
2014年 | 2768篇 |
2013年 | 8272篇 |
2012年 | 5851篇 |
2011年 | 7256篇 |
2010年 | 4895篇 |
2009年 | 4744篇 |
2008年 | 6595篇 |
2007年 | 6698篇 |
2006年 | 6405篇 |
2005年 | 5914篇 |
2004年 | 5395篇 |
2003年 | 4737篇 |
2002年 | 4591篇 |
2001年 | 5921篇 |
2000年 | 4506篇 |
1999年 | 3655篇 |
1998年 | 2853篇 |
1997年 | 2930篇 |
1996年 | 2826篇 |
1995年 | 2618篇 |
1994年 | 2484篇 |
1993年 | 2373篇 |
1992年 | 2863篇 |
1991年 | 2719篇 |
1990年 | 2652篇 |
1989年 | 2705篇 |
1988年 | 2631篇 |
1987年 | 2614篇 |
1986年 | 2431篇 |
1985年 | 3309篇 |
1984年 | 3317篇 |
1983年 | 2731篇 |
1982年 | 2950篇 |
1981年 | 2872篇 |
1980年 | 2776篇 |
1979年 | 2916篇 |
1978年 | 3157篇 |
1977年 | 2976篇 |
1976年 | 2904篇 |
1975年 | 2775篇 |
1974年 | 2712篇 |
1973年 | 2731篇 |
1972年 | 1765篇 |
1971年 | 1474篇 |
1968年 | 1943篇 |
1967年 | 2132篇 |
1966年 | 1922篇 |
1965年 | 1499篇 |
排序方式: 共有10000条查询结果,搜索用时 78 毫秒
51.
Development and validation of a reversed‐phase HPLC method for CYP1A2 phenotyping by use of a caffeine metabolite ratio in saliva
下载免费PDF全文
![点击此处可从《Biomedical chromatography : BMC》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Elias Begas Evangelos Kouvaras Andreas K. Tsakalof Maria Bounitsi Eftihia Konstadinos Asprodini 《Biomedical chromatography : BMC》2015,29(11):1657-1663
CYP1A2 is important for metabolizing various clinically used drugs. Phenotyping of CYP1A2 may prove helpful for drug individualization therapy. Several HPLC methods have been developed for quantification of caffeine metabolites in plasma and urine. Aim of the present study was to develop a valid and simple HPLC method for evaluating CYP1A2 activity during exposure in xenobiotics by the use of human saliva. Caffeine and paraxanthine were isolated from saliva by liquid‐liquid extraction (chlorophorm/isopropanol 85/15v/v). Extracts were analyzed by reversed‐phase HPLC on a C18 column with mobile phase 0.1% acetic acid/methanol/acetonitrile (80/20/2 v/v) and detected at 273nm. Caffeine and paraxanthine elution times were <13min with no interferences from impurities or caffeine metabolites. Detector response was linear (0.10–8.00µg/ml, R2>0.99), recovery was >93% and bias <4.47%. Intra‐ and inter‐day precision was <5.14% (n=6). The limit of quantitation was 0.10µg/ml and the limit of detection was 0.018±0.002µg/mL for paraxanthine and 0.032±0.002µg/ml for caffeine. Paraxanthine/caffeine ratio of 34 healthy volunteers was significantly higher in smokers (p<0.001). Saliva paraxanthine/caffeine ratios and urine metabolite ratios were highly correlated (r=0.85, p<0.001). The method can be used for the monitoring of CYP1A2 activity in clinical practice and in studies relevant to exposure to environmental and pharmacological xenobiotics. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
52.
53.
54.
55.
Briana L. Simms Nan Ji Indika Chandrasiri Mohammad Farid Zia Chinwe S. Udemgba Ravinder Kaur Jared H. Delcamp Alex Flynt Chalet Tan Davita L. Watkins 《Journal of polymer science. Part A, Polymer chemistry》2021,59(19):2177-2192
Here, we demonstrate the applicability of self-assembling linear-dendritic block copolymers (LDBCs) and their nanoaggregates possessing varied surfaces as therapeutic nanocarriers. These LDBCs are comprised of a hydrophobic, linear polyester chemically coupled to a hydrophilic dendron polyamidoamine (PAMAM)—the latter of which acts as the surface of the self-assembled nanoaggregate in aqueous media. To better understand how surface charge density affects the overall operability of these nanomaterials, we modified the nanoaggregate surface to yield cationic (NH3+), neutral (OH), and anionic (COO−) surfaces. The effect of these modifications on the physicochemical properties (i.e., size, morphology, and surface charge density), colloidal stability, and cellular uptake mechanism of the polymeric nanocarrier were investigated. This comparative study demonstrates the viability of nanoaggregates formed from PDLLA-PAMAM LDBCs to serve as nanocarriers for applications in drug delivery. 相似文献
56.
Kinetics and Catalysis - Boron and barium were employed as dopants for the VMgO system. The catalysts were characterized by ICP-OES, BET, IR, powder XRD, EDX, TPR-H2, TPD-NH3, XPS, and 51V MAS NMR.... 相似文献
57.
Chris H. Hill Agnete H. Viuff Samantha J. Spratley Stéphane Salamone Stig H. Christensen Randy J. Read Nigel W. Moriarty Henrik H. Jensen Janet E. Deane 《Chemical science》2015,6(5):3075-3086
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
58.
59.
60.
Experimental Mechanics - Insufficient data are available to fully understand the effects of metal additive manufacturing (AM) defects for widespread adoption of the emerging technology.... 相似文献