全文获取类型
收费全文 | 5381篇 |
免费 | 427篇 |
国内免费 | 267篇 |
出版年
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.
Li M Li S Lou Z Liao X Zhao X Meng Z Bartlam M Rao Z 《Journal of structural biology》2008,162(2):229-236
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.
Atsumi S Cann AF Connor MR Shen CR Smith KM Brynildsen MP Chou KJ Hanai T Liao JC 《Metabolic engineering》2008,10(6):305-311
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), 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.
A study on the fundamental factors determining the efficacy of siRNAs with high C/G contents 总被引:1,自引:0,他引:1
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.
Boscolo R Liao JC Roychowdhury VP 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2008,5(1):15-24
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.
Nawarak J Huang-Liu R Kao SH Liao HH Sinchaikul S Chen ST Cheng SL 《Journal of proteome research》2008,7(9):3737-3746
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.