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   2415篇
  免费   88篇
  国内免费   100篇
  2023年   6篇
  2022年   19篇
  2021年   19篇
  2020年   30篇
  2019年   34篇
  2018年   57篇
  2017年   55篇
  2016年   39篇
  2015年   51篇
  2014年   116篇
  2013年   201篇
  2012年   99篇
  2011年   191篇
  2010年   170篇
  2009年   143篇
  2008年   152篇
  2007年   169篇
  2006年   116篇
  2005年   87篇
  2004年   102篇
  2003年   72篇
  2002年   69篇
  2001年   56篇
  2000年   36篇
  1999年   37篇
  1998年   32篇
  1997年   33篇
  1996年   40篇
  1995年   22篇
  1994年   22篇
  1993年   19篇
  1992年   11篇
  1991年   24篇
  1990年   16篇
  1989年   11篇
  1988年   22篇
  1987年   22篇
  1986年   7篇
  1985年   32篇
  1984年   19篇
  1983年   22篇
  1982年   37篇
  1981年   17篇
  1980年   21篇
  1979年   19篇
  1978年   10篇
  1977年   5篇
  1976年   7篇
  1973年   2篇
  1972年   2篇
排序方式: 共有2603条查询结果,搜索用时 15 毫秒
1.
S-Adenosyl-L -methionine (SAM) is an essential metabolite in all living organisms. In clinical research, SAM has also been suggested as a chemotherapeutic agent in various diseases. The main problem of SAM is its instability at high temperatures, at neutral and alkaline pH, and in the presence of humidity. SAM retention in spray-dried powder was determined under various conditions of spray-drying. The highest SAM retention was obtained when maltodextrin (dextrose equivalent, DE, of 25) was used as the carrier solid with the SAM feed liquid at pH 4.0. The water content in the powder had a significant effect on the stability of SAM. SAM powder with lower water content exhibited higher stability.  相似文献   
2.
Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 (∼ 90 μM). Their IC50 values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon’s plot; however, the inhibition mechanism of endometase was noncompetitive with a Ki value of 240 μM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity.  相似文献   
3.
Here, we seek to determine how compliantly suspended loads could affect the dynamic stability of legged locomotion. We theoretically model the dynamic stability of a human carrying a load using a coupled spring-mass-damper model and an actuated spring-loaded inverted pendulum model, as these models have demonstrated the ability to correctly predict other aspects of locomotion with a load in prior work, such as body forces and energetic cost. We report that minimizing the load suspension natural frequency and damping ratio significantly reduces the stability of the load mass but may slightly improve the body stability of locomotion when compared to a rigidly attached load. These results imply that a highly-compliant load suspension could help stabilize body motion during human, animal, or robot load carriage, but at the cost of a more awkward (less stable) load.  相似文献   
4.
Two glutamic acid-rich fusion peptide analogs of influenza hemagglutinin were synthesized to study the organization of the charged peptides in the membranous media. Fluorescence and gel electrophoresis experiments suggested a loose association between the monomers in the vesicles. A model was built which showed that a positional difference of 3, 7 and 4, 8 results in the exposure of Glu3 and Glu7 side chains to the apolar lipidic core. Supportive results include: first, pKa values of two pH units higher than reference value in aqueous medium for Glu3 and Glu7 CγH, whereas the deviation of pKa from the reference value for Glu4 and Glu8 CγH is substantially smaller; second, Hill coefficients of titration shift of these protons indicate anti-cooperativity for Glu3 and Glu7 side chain protons but less so for Glu4 and Glu8, implying a strong electrostatic interaction between Glu3 and Glu7 possibly resulting from their localization in an apolar environment; third, positive and larger titration shift for NH of Glu3 is observed compared to that of Glu4, suggesting stronger hydrogen bond between the NH and the carboxylic group of Glu3 than that of Glu4, consistent with higher degree of exposure to hydrophobic medium for the side chain of Glu3.  相似文献   
5.
Genistein (GEN) has been previously shown to have a proapoptotic effect on cancer cells through a p53-dependent pathway, the mechanism of which remains unclear. One of its intracellular targets, APE1, protects against apoptosis under genotoxic stress and interacts with p53. In this current study, we explored the mechanism of the proapoptotic effect of GEN by examining the APE1–p53 protein–protein interaction. We initially showed that the p53 protein level was elevated in GEN-treated human non-small lung cancer A549 cells and cervical cancer HeLa cells. By examining both protein synthesis and degradation, we found that GEN enhances p53 intracellular stability by interfering with the interaction of APE1 and p53, which provided a plausible explanation for how GEN initiates apoptosis. Furthermore, we found that the interaction between APE1 and p53 is important for the degradation of p53 and is dependent on the redox domain of APE1 by utilizing the redox domain mutant APE1 C65A. Our data suggest that the degradation of wild-type p53 is blocked when the redox domain of APE1 is masked or interrupted. Based on this evidence, we hereby report a novel mechanism of p53 degradation through an APE1-mediated, redox-dependent pathway.  相似文献   
6.
Two mutants that grew faster than the wild-type (WT) strain under high light conditions were isolated from Synechocystis sp. strain PCC 6803 transformed with a transposon-bearing library. Both mutants had a tag in ssl1690 encoding NdhO. Deletion of ndhO increased the activity of NADPH dehydrogenase (NDH-1)-dependent cyclic electron transport around photosystem I (NDH-CET), while overexpression decreased the activity. Although deletion and overexpression of ndhO did not have significant effects on the amount of other subunits such as NdhH, NdhI, NdhK, and NdhM in the cells, the amount of these subunits in the medium size NDH-1 (NDH-1M) complex was higher in the ndhO-deletion mutant and much lower in the overexpression strain than in the WT. NdhO strongly interacts with NdhI and NdhK but not with other subunits. NdhI interacts with NdhK and the interaction was blocked by NdhO. The blocking may destabilize the NDH-1M complex and repress the NDH-CET activity. When cells were transferred from growth light to high light, the amounts of NdhI and NdhK increased without significant change in the amount of NdhO, thus decreasing the relative amount of NdhO. This might have decreased the blocking, thereby stabilizing the NDH-1M complex and increasing the NDH-CET activity under high light conditions.  相似文献   
7.
A mathematical model of the linearized growth curve and its physiological interpretation by the introduction of proper age, which is proportional to the chronological age, are presented here. In the second phase, but not in the first phase, this constant of proportionality is highly correlated with the age at menarche.  相似文献   
8.
Summary A 2 m DNA-like plasmid, pSR1, isolated from a strain of Zygosaccharomyces rouxii has three coding frames, P, S and R. Insertional inactivation of R completely abolished the intramolecular recombination, and the defect was complemented by an intact R frame on a coexistent plasmid molecule. The P and S regions were also transactive and important, but not essential, for the stable maintenance of the plasmid molecules. Insertional disruption of the P frame suggested that it produces a protein factor. Similar insertional disruption of the S frame affected the plasmid stability in Z. rouxii and Saccharomyces cerevisiae hosts differently, depending on whether the inserted DNA fragment was a short 8 bp SalI linker or a long (2.2 kb) DNA fragment. Results strongly suggested that the S region encodes two factors, one RNA and the other a protein, and that the S protein is compatible with a sprecific hostfactor in Z. rouxii, but not in S. cerevisiae. In addition, a cis-acting locus, Z, was found at a site in the plasmid molecule where no distinct open reading frames were located. No long direct repeats or inverted repeats were observed in the Z region, such as are found in the REP3 locus of 2 m DNA.  相似文献   
9.
Scavenging of superoxide radical by ascorbic acid   总被引:1,自引:0,他引:1  
Using acetaldehyde and xanthine oxidase as the source of suPeroxide radical, the second order rate constant for the reaction between ascorbic acid and superoxide radical was estimated to be 8.2 X 107 M-1 s-1. In rats, the average tissue concentration of ascorbic acid was of the order of 10-3 M and that of superoxide dismutase was of the order of 10-6 M. So, taking together both the rate constants and the tissue concentrations, the efficacy of ascorbic acid for scavenging superoxide radical in animal tissues appears to be better than that of suPeroxide dismutase. The significance of ascorbic acid as a scavenger of superoxide radical has been discussed from the point of view of the evolution of ascorbic acid synthesizing capacity of terrestrial vertebrates.  相似文献   
10.
白纹伊蚊幼虫龄期的发育历期   总被引:2,自引:0,他引:2  
在实验室内20±1℃, 23±1℃, 25±1℃, 28±1℃和30±1℃恒温条件下, 观察了白纹伊蚊(Aedes albopictus)幼虫(广州株)的发育历期.幼虫的总发育历期和各龄幼虫的发育历期随温度的上升而缩短, 各龄幼虫历期在总发育历期中占有恒定的百分比, 据此计算出其捕获机率.各龄幼虫的发育历期与温度呈直线回归关系.通过积温公式, 求出各龄幼虫的积温常数.此外还探索了营养对幼虫发育历期的影响, 从而影响各龄幼虫捕获机率的计算.  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