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   5381篇
  免费   427篇
  国内免费   267篇
  2023年   50篇
  2022年   105篇
  2021年   253篇
  2020年   175篇
  2019年   207篇
  2018年   188篇
  2017年   135篇
  2016年   211篇
  2015年   341篇
  2014年   384篇
  2013年   414篇
  2012年   504篇
  2011年   443篇
  2010年   270篇
  2009年   243篇
  2008年   267篇
  2007年   242篇
  2006年   189篇
  2005年   175篇
  2004年   166篇
  2003年   120篇
  2002年   108篇
  2001年   106篇
  2000年   93篇
  1999年   99篇
  1998年   40篇
  1997年   51篇
  1996年   41篇
  1995年   38篇
  1994年   29篇
  1993年   33篇
  1992年   41篇
  1991年   37篇
  1990年   46篇
  1989年   36篇
  1988年   23篇
  1987年   24篇
  1986年   13篇
  1985年   14篇
  1984年   10篇
  1983年   10篇
  1982年   9篇
  1981年   8篇
  1979年   14篇
  1978年   8篇
  1975年   5篇
  1973年   9篇
  1972年   6篇
  1971年   9篇
  1968年   5篇
排序方式: 共有6075条查询结果,搜索用时 15 毫秒
941.
厦门同安湾定置网捕获鱼类的多样性及营养级特征   总被引:1,自引:0,他引:1  
利用2012年4月至2013年3月在同安湾进行的定置网渔业资源调查资料, 探讨了该海域鱼类多样性及平均营养级特征。结果表明, 周年逐月共鉴定鱼类112种, 隶属于15目53科88属。渔获物组成以沿岸小型底层鱼类为主, 其中中上层鱼类15种, 中下层鱼类18种, 底层鱼类79种; 暖水性种类84种, 暖温性种类28种, 亚热带动物区系特征明显; 杂食性鱼类8种, 低级肉食性鱼类71种, 中级肉食性鱼类30种, 高级肉食性鱼类3种, 以低级肉食性鱼类为主。中华海鲶(Tachysurus sinensis)是夏、秋、冬三季的优势种, 六指多指马鲅(Polydactylus sextarius)、锯脊塘鳢(Butis koilomatodon)和髭缟鰕虎鱼(Tridentiger barbatus)是春、冬两季的优势种。重量和尾数多样性指数最高值均在11月, 分别为3.26和3.29; 最低值均在2月, 分别为1.78和1.77。鱼类种类存在明显的季节更替现象, 其月更替率6月最低, 为40.1%; 3月最高, 达68.6%。鱼类平均营养级也存在明显的季节变化, 其中3月最低, 为3.02; 1月最高, 为3.92; 周年平均营养级为3.52。与2003年调查资料相比, 鱼类种类数明显减少, 鱼类组成和优势种发生了很大的变化, 导致变化的主要原因可能是过度捕捞、栖息地破坏和环境污染等。  相似文献   
942.
Transgelin (TAGLN), also known as smooth muscle protein 22 (SM22), is a highly conserved protein found in smooth muscle tissues of adult vertebrates. Abolition of transgelin gene expression by the oncogenic Ras may be an important early event in tumor progression and a diagnostic marker for breast and colon cancer development. Transgelin contains a single calponin homology (CH) domain. However, the question of whether this single CH domain can bind actin remains open. Here we report the 2.3 A resolution crystal structure of full length human transgelin, whose main structural feature is confirmed to be a CH domain. Secondary structures of CH domains from different proteins were analyzed and conserved residues were identified that maintain similar tertiary structures.  相似文献   
943.
Compared to ethanol, butanol offers many advantages as a substitute for gasoline because of higher energy content and higher hydrophobicity. Typically, 1-butanol is produced by Clostridium in a mixed-product fermentation. To facilitate strain improvement for specificity and productivity, we engineered a synthetic pathway in Escherichia coli and demonstrated the production of 1-butanol from this non-native user-friendly host. Alternative genes and competing pathway deletions were evaluated for 1-butanol production. Results show promise for using E. coli for 1-butanol production.  相似文献   
944.
Deleted in liver cancer-1 (DLC-1): a tumor suppressor not just for liver   总被引:1,自引:0,他引:1  
Deleted in liver cancer 1 (DLC-1), as its name implied, was originally isolated as a potential tumor suppressor gene often deleted in hepatocellular carcinoma. Further studies have indicated that down-expression of DLC-1 either by genomic deletion or DNA methylation is associated with a variety of cancer types including lung, breast, prostate, kidney, colon, uterus, ovary, and stomach. Re-expression of DLC-1 in cancer cells regulates the structure of actin cytoskeleton and focal adhesions and significantly inhibits cell growth, supporting its role as a tumor suppressor. This tumor suppressive function relies on DLC-1's RhoGTPase activating protein (RhoGAP) activity and steroidogenic acute regulatory (StAR)-related lipid transfer (START) domain, as well as its focal adhesion localization, which is recruited by the Src Homology 2 (SH2) domains of tensins in a phosphotyrosine-independent fashion. Therefore, the expression and subcellular localization of DLC-1 could be a useful molecular marker for cancer prognosis, whereas DLC-1 and its downstream signaling molecules might be therapeutic targets for the treatment of cancer.  相似文献   
945.
Aims: Adenosine triphosphate (ATP) during the enzymatic production of glutathione is necessary. In this study, our aims were to investigate the reason for low glutathione production in Escherichia coli coupled with an ATP regeneration system and to develop a new strategy to improve the system. Methods and Results: Glutathione can be synthesized by enzymatic methods in the presence of ATP and three precursor amino acids (l ‐glutamic acid, l ‐cysteine and glycine). In this study, glutathione was produced from E. coli JM109 (pBV03) coupled with an ATP regeneration system, by using glycolytic pathway of Saccharomyces cerevisiae WSH2 as ATP regenerator from adenosine and glucose. In the coupled system, adenosine used for ATP regeneration by S. cerevisiae WSH2 was transformed into hypoxanthine irreversibly by E. coli JM109 (pBV03). As a consequence, S. cerevisiae WSH2 could not obtain enough adenosine for ATP regeneration in the glycolytic pathway in spite of consuming 400 mmol l?1 glucose within 1 h. By adding adenosine deaminase inhibitor to block the metabolism from adenosine to hypoxanthine, glutathione production (8·92 mmol l?1) enhanced 2·74‐fold in the coupled system. Conclusions: This unusual phenomenon that adenosine was transformed into hypoxanthine irreversibly by E. coli JM109 (pBV03) revealed that less glutathione production in the coupled ATP regeneration system was because of the poor efficiency of ATP generation. Significance and Impact of the Study: The results presented here provide a strategy to improve the efficiency of the coupled ATP regeneration system for enhancing glutathione production. The application potential can be microbial processes where ATP is needed.  相似文献   
946.
Bilirubin, an antioxidant in the blood, plays a role in protection from atherosclerosis. The level of bilirubin is highly correlated to the incidence of coronary artery disease (CAD). Unconjugated bilirubin is conjugated with glucuronic acid through the reaction of uridine 5′-diphosphate-glucuronosyl transferase 1A1 (UGT1A1). The interactions of CAD and the variations in the coding regions of the UGT1A1 gene have never been evaluated. The purpose of this study was to analyze the influence of the UGT1A1 variant on the incidence of CAD. There were 135 participants in this study: 61 in the experimental group, who had CAD, and 74 in the control group, who did not have CAD. The blood samples from all 135 participants were collected and assayed to clarify the relationship between bilirubin and CAD. The assay of the polymerase chain reaction and the sequence of the UGT1A1 gene were examined to find the gene’s polymorphisms. The bilirubin levels for the participants in the control group were significantly higher than for the patients in the CAD group. Although the concentration of bilirubin in the UGT1A1 variant was higher than the wild type for the patients in the CAD group, there was no significant difference in the polymorphism of UGT1A1 between the patients in the CAD group and the participants in the control group.  相似文献   
947.
Although there are many reports about the efficacy of siRNAs, it is not clear whether those siRNAs with high C/G contents can be used to silence their target mRNAs efficiently. In this study, we investigated the structure and function of a group of siRNAs with high C/G contents. The results showed that single siRNAs against the Calpain, Otoferlin and Her2 mRNAs could induce different silencing effects on their targets, suggesting that the accessibility to target sequences influences the efficacy of siRNA. Unexpectedly, a single siRNA could target its cognate sequence in the 3’UTR of EEF1D or the 5’UTR of hTRF2 or CDC6. Their interaction induced different modes of gene silencing. Furthermore, the introduction of mutations into the 3’ end of the passenger strand showed that the position and number of mutated nucleotides could exert some influence on the efficacy of siRNA. However, these mutations did not completely block the passenger strand from exerting its RNAi effect. Interestingly, our findings also indicated that the target mRNA might play essential roles in maintaining or discarding the guide strand in RISCs. Thus, the conclusion could be drawn that favorable siRNA sequences, accessible target structures and the fast cleavage mode are necessary and sufficient prerequisites for efficient RNAi.  相似文献   
948.
In this article, we introduce an exploratory framework for learning patterns of conditional co-expression in gene expression data. The main idea behind the proposed approach consists of estimating how the information content shared by a set of M nodes in a network (where each node is associated to an expression profile) varies upon conditioning on a set of L conditioning variables (in the simplest case represented by a separate set of expression profiles). The method is non-parametric and it is based on the concept of statistical co-information, which, unlike conventional correlation based techniques, is not restricted in scope to linear conditional dependency patterns. Moreover, such conditional co-expression relationships can potentially indicate regulatory interactions that do not manifest themselves when only pair-wise relationships are considered. A moment based approximation of the co-information measure is derived that efficiently gets around the problem of estimating high-dimensional multi-variate probability density functions from the data, a task usually not viable due to the intrinsic sample size limitations that characterize expression level measurements. By applying the proposed exploratory method, we analyzed a whole genome microarray assay of the eukaryote Saccharomices cerevisiae and were able to learn statistically significant patterns of conditional co-expression. A selection of such interactions that carry a meaningful biological interpretation are discussed.  相似文献   
949.
Although the toxicogenomics of kojic acid treated A375 human malignant melanoma cells has been elucidated, the proteomics of cellular response is still poorly understood. We performed proteomic analysis to investigate the anticancer effect of kojic acid on protein expression profile in A375 cells. A375 cells were treated with kojic acid at 8 microg/mL for 24, 48, and 72 h. With the use of 2-D PAGE and MALDI-Q-TOF MS and MS/MS analyses, proteomic profiles of A375 cells between control and kojic acid treatment were compared, and 30 differentially expressed proteins, containing 2 up-regulated proteins and 28 down-regulated proteins, were identified. Among these proteins, 17 isoforms of 5 identical proteins were observed and 11 chaperone proteins showed the high proportion of protein spots with 36.7% of total proteins. Bioinformatic tools were used to search for protein function and prediction of protein interaction. Sixteen differentially expressed proteins exhibited interaction network linked to the downstream regulations of p53 tumor suppressor and cell apoptosis, which may lead to suppress the melanogenesis and tumorigenesis of kojic acid treated A375 cells. In addition, GRP75, VIME and 2AAA were validated by Western blot analysis, whereas GRP75, 2AAA, HS90B, ENPL and KPYM were validated by RT-PCR. Therefore, these proteins play the important roles in cancer progression and may be potential biomarkers that are useful for diagnostic and therapeutic applications of malignant melanoma cancer.  相似文献   
950.
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