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   18871篇
  免费   1698篇
  国内免费   1444篇
  22013篇
  2023年   244篇
  2022年   533篇
  2021年   897篇
  2020年   607篇
  2019年   688篇
  2018年   727篇
  2017年   539篇
  2016年   702篇
  2015年   1150篇
  2014年   1273篇
  2013年   1369篇
  2012年   1566篇
  2011年   1501篇
  2010年   981篇
  2009年   833篇
  2008年   909篇
  2007年   876篇
  2006年   775篇
  2005年   657篇
  2004年   619篇
  2003年   545篇
  2002年   517篇
  2001年   392篇
  2000年   390篇
  1999年   359篇
  1998年   169篇
  1997年   162篇
  1996年   158篇
  1995年   119篇
  1994年   146篇
  1993年   91篇
  1992年   155篇
  1991年   147篇
  1990年   122篇
  1989年   98篇
  1988年   82篇
  1987年   96篇
  1986年   83篇
  1985年   92篇
  1984年   48篇
  1983年   48篇
  1982年   48篇
  1981年   36篇
  1980年   37篇
  1979年   52篇
  1978年   41篇
  1977年   45篇
  1976年   33篇
  1975年   35篇
  1974年   44篇
排序方式: 共有10000条查询结果,搜索用时 7 毫秒
991.
Blocks of tissue were removed from various locations in the bovine digestive tract and fixed and processed for transmission and scanning electron microscopy by techniques that retained adherent bacteria. The distribution of bacteria on the surface of epithelial cells was examined by scanning electron microscopy. This showed intermittent colonization of the epithelia with the formation of occasional microcolonies of morphologically similar bacterial cells. Transmission electron microscopy of ruthenium red-stained material showed the presence of both the glycocalyx of the bovine epithelial cells and fibrous carbohydrate coats surrounding adherent bacteria. The carbohydrate coats appeared to mediate the attachment of bacteria to the epithelium, to food particles, and to each other so that microcolonies were formed. Careful examination of the bacterial colonization of keratinized cells in the process of being sloughed from the surface of the stratified squamous epithelium of the rumen showed that these dead cells were digested by adherent bacteria of a limited number of morphological types. The spatial relationship of this mixed, adherent, microbial population to living and dead epithelial cells and to food particles indicates that digestive processes of some importance may be accomplished by this stationary component of the microbial flora of the digestive tract.  相似文献   
992.

Background

We have previously reported a novel fungal galectin Agrocybe aegerita lectin (AAL) with apoptosis-induced activity and nuclear migration activity. The importance of nuclear localization for AAL's apoptosis-induced activity has been established by mutant study. However, the mechanism remains unclear.

Methods

We further investigated the mechanism using a previously reported carbohydrate recognition domain (CRD) mutant protein H59Q, which retained its nuclear localization activity but lost most of its apoptotic activity. The cell membrane-binding ability of recombinant AAL (rAAL) and H59Q was analyzed by FACS, and their cellular partners were identified by affinity chromatography and mass spectroscopy. Furthermore, the interaction of AAL and ligand was proved by mammalian two-hybrid and pull down assays. A knockdown assay was used to confirm the role of the ligand.

Results

The apoptotic activity of AAL could be blocked by lactose. Mutant H59Q retained comparable cell membrane-binding ability to rAAL. Four cellular binding partners of AAL in HeLa cells were identified: glucose-regulated protein 78 (GRP78); mortality factor 4-like protein 1 (MRG15); elongation factor 2 (EEF2); and heat shock protein 70 (Hsp70). CRD region of AAL was required for the interaction between AAL/mutant AAL and MRG15. MRG15 knockdown increased the cells' resistance to AAL treatment.

Conclusion

MRG15 was a nuclear ligand for AAL in HeLa cells. These data implied the existence of a novel nuclear pathway for the antitumor activity of fungal galectin AAL.

General significance

These findings provide a novel explanation of AAL bioactivity and contribute to the understanding of mushroom lectins' antitumor activity.  相似文献   
993.
A multi‐component catalyst Ni‐VOx/AC (VOx is comprised of V2O5 and VO2, x = 2.18) was synthesized by a wet impregnation method. The synthesized Ni‐VOx/AC shows a superior catalytic effect on de/hydrogenation of Mg. The MgH2+Ni‐VOx/AC composites can absorb 6.2 wt.‐% hydrogen within only 1 min at 150 °C under a hydrogen pressure of 2 MPa and desorb 6.5 wt.‐% hydrogen within 10 min at 300 °C under an initial hydrogen pressure of 1 KPa, which overcomes a critical barrier for practical use of Mg as a hydrogen storage material. A significant decrease of activation energy (Ea) indicates that Ni‐VOx/AC catalyst is highly efficient for Mg de/hydrogenation, which may be ascribed to the synergistic effect of bimetals (metal oxides) and nanocarbon.  相似文献   
994.

Background

Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2∼10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia.

Methodology/Principal Findings

In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20∼50 SNPs reported by the remaining individual GWA studies explained 3∼5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent.

Conclusions/Significance

We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.  相似文献   
995.
黄肉桃种质资源的RAPD分析   总被引:19,自引:0,他引:19  
利用RAPD技术,采用从200个十碱基随机物筛选的22个随机引物对37个黄肉桃品种的基因组DNA进行扩增,通过扩增的180个位点的谱带的聚类,分析供试黄肉桃的系统发育,运用特殊谱带,建立了黄肉桃的分子检索表,并提出了重点保存的黄肉桃种质。  相似文献   
996.
The tal-1 gene is altered as a consequence of the t(1;14) (p32;q11) chromosome translocation observed in 3% of patients with T cell acute lymphoblastic leukemia (T-ALL). tal-1 encodes a helix-loop-helix (HLH) domain, a DNA binding and dimerization motif found in a number of proteins involved in cell growth and differentiation. We now report that an additional 25% of T-ALL patients bear tal-1 gene rearrangements that are not detected by karyotype analysis. These rearrangements result from a precise 90 kb deletion (designated tald) that arises independently in different patients by site-specific DNA recombination. Since the deletion junctions resemble the coding joints of assembled immunoglobulin genes, tald rearrangements are likely to be mediated by aberrant activity of the immunoglobulin recombinase. Moreover, t(1;14)(p32;q11) translocations and tald rearrangements disrupt the coding potential of tal-1 in an equivalent manner, and thereby generate a common genetic lesion shared by a significant proportion of T-ALL patients.  相似文献   
997.
998.
This study aimed to validate the methylation of key genes in hepatocellular carcinoma (HCC) screened by bioinformatics analysis and explore whether they affected HCC cell proliferation, migration, and invasion. Using The Cancer Genome Atlas (TCGA) database, HCC-related differentially methylated positions (DMPs) were screened, genes corresponding to DMPs were selected, and prognosis-related genes were identified. A representative DMP was used to divide the DMPs into hyper- and hypomethylated groups. Expression of key genes in cell lines was detected using quantitative real-time polymerase chain reaction and western blot analysis. After treatment of HepG2 cells with 5-Aza-2′-deoxycytidine (5-Aza-DC), gene expression was observed. Bisulfite sequencing PCR assay was used to detect methylation frequency. Overexpressed GRASP lentiviral vectors were constructed to analyze their influence on cell proliferation, migration, and invasion using cell counting kit-8 and transwell assays. Forty-three HCC prognosis-related genes were screened using the TCGA database. cg00249511 (SCT) was used to divide the DMPs into hyper- and hypomethylated groups, distinguishing between high- and low-risk samples. The prognosis survival model constructed using 12 genes revealed the prognosis type. GRASP messenger RNA was downregulated in HepG2 and upregulated after 5-Aza-DC treatment. In HCC tissues, methylation frequency of GRASP was upregulated. GRASP overexpression inhibited HepG2 cell proliferation, invasion, and G-CSFR expression. Thus, GRASP might be a prognosis-related gene controlled by methylation.  相似文献   
999.
1000.
Biomechanics and Modeling in Mechanobiology - Due to ethical reasons, piglets have often been employed as surrogates for children in biomechanics studies. To our knowledge, no public data detailing...  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