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   223篇
  免费   7篇
  国内免费   1篇
  2023年   1篇
  2022年   1篇
  2021年   1篇
  2020年   1篇
  2019年   1篇
  2018年   1篇
  2016年   3篇
  2015年   5篇
  2014年   3篇
  2013年   3篇
  2012年   17篇
  2011年   16篇
  2010年   5篇
  2009年   12篇
  2008年   18篇
  2007年   21篇
  2006年   15篇
  2005年   17篇
  2004年   10篇
  2003年   7篇
  2002年   9篇
  2001年   6篇
  2000年   1篇
  1999年   4篇
  1998年   2篇
  1996年   1篇
  1992年   4篇
  1991年   3篇
  1990年   3篇
  1989年   5篇
  1988年   3篇
  1987年   4篇
  1986年   3篇
  1985年   3篇
  1984年   5篇
  1983年   5篇
  1982年   1篇
  1981年   1篇
  1980年   1篇
  1979年   4篇
  1978年   1篇
  1976年   1篇
  1975年   1篇
  1973年   1篇
  1971年   1篇
排序方式: 共有231条查询结果,搜索用时 281 毫秒
11.
12.
The establishment of protected areas is traditionally considered indispensable to preserve biodiversity hotspots or areas inhabited by threatened species. The analysis of correlations between composition or richness of several taxonomic groups in a specific area has emerged as a useful mechanism to quickly identify areas of biological and conservation interest, and is currently used to select and design protected areas. The effect of habitat fragmentation on these correlations at a regional scale has been studied, but the effect of land use on the correlations obtained at local scale is poorly understood. We evaluated the relationships among different taxonomic groups frequently used in biological assessments for reserve design (vascular flora, amphibians, reptiles, birds and mammals), taking into account the effects of land use on these correlations. We compared richness and species composition of these groups in 1 km2 quadrants within a total area of 75 km2 in a low mountain Mediterranean area. Richness and composition were significantly correlated between several groups, both using the complete data set and also analyzing natural and disturbed areas separately. Species composition and species richness correlations were not congruent at the full landscape approach, nor natural and disturbed quadrants. Factors extrinsic to the communities also varied their influence in the assemblage of the community and species richness or not land uses were taken into account. According to our results, natural and human-disturbed areas should not be combined in cross-taxon congruences analysis at local scale.  相似文献   
13.

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   
14.
The interleukin-6 (IL-6) stimulates growth in cells such as multiple myeloma and B-cell plasmacytomas/hybridomas, while it inhibits growth in several myeloid leukemia cells. The IL-6 receptor has subunit called gp130. It was reported that Ser-782 of gp130 is phosphorylated by unidentified kinase(s) in cell extracts, and level of gp130 (S782A) transiently expressed on the cell surface of COS-7 is 6-times higher than that of the wild type. These results motivated us to analyze whether the phosphorylation of gp130 at Ser-782 is involved in its degradation or not. In this study, we demonstrated here that treatment of HepG2 cells with okadaic acid (OA), a potent inhibitor for PP2A, promotes phosphorylation of gp130 at Ser-782 and degradation of gp130. MG115, a proteasome inhibitor, suppressed this degradation. These effects of OA could not be replaced with tautomycetin (TC), an inhibitor for PP1. Purified PP2A dephosphorylated phospho-Ser-782 of gp130 in vitro. IL-6-induced activation of Stat3 was suppressed by preincubation of the cells with OA, suggesting that the IL-6 signaling pathway was blocked by OA through degradation of gp130. Taken together, present results strongly suggest that degradation of gp130 is regulated through a phosphorylation-dephosphorylation mechanism in which PP2A is crucially involved and that gp130 is a potential therapeutic target in cancers. (Mol Cell Biochem 269: 183–187, 2005)  相似文献   
15.
Normal neurological function depends on a constant supply of polyunsaturated fatty acids to the brain. A considerable proportion of essential fatty acids originates from lipoprotein-associated lipids that undergo uptake and/or catabolism at the blood-brain barrier (BBB). This study aimed at identifying expression and regulation of endothelial lipase (EL) in brain capillary endothelial cells (BCEC), major constituents of the BBB. Our results revealed that BCEC are capable of EL synthesis and secretion. Overexpression of EL resulted in enhanced hydrolysis of extracellular high-density lipoprotein (HDL)-associated sn-2-labeled [(14)C]20 : 4 phosphatidylcholine. [(14)C]20 : 4 was recovered in cellular lipids, indicating re-uptake and intracellular re-esterification. To investigate local regulation of EL in the cerebrovasculature, BCEC were cultured in the presence of peroxisome-proliferator activated receptor (PPAR)- and liver X receptor (LXR)-agonists, known to regulate HDL levels. These experiments revealed that 24(S)OH-cholesterol (a LXR agonist), bezafibrate (a PPARalpha agonist), or pioglitazone (a PPARgamma agonist) resulted in down-regulation of EL mRNA and protein levels. Our findings implicate that EL could generate fatty acids at the BBB for transport to deeper regions of the brain as building blocks for membrane phospholipids. In addition PPAR and LXR agonists appear to contribute to HDL homeostasis at the BBB by regulating EL expression.  相似文献   
16.
In our previous work we showed that 3F10 monoclonal antibody (mAb), which recognizes the rat complement receptor 1-related/gene protein y (Crry), induces homotipic aggregation of thymocytes. In this work we studied the effect of 3F10 mAb on proliferation of rat thymocytes stimulated with concanavalin A (ConA) or by cross-linking the T cell receptor (TCR) by anti-alphabetaTCR mAb (R73), in vitro, and the mechanisms involved in the process. Our results show that 3F10 mAb stimulates proliferation of total thymocytes triggered by suboptimal concentrations of ConA or TCR cross-linking, in a dose-dependent manner. Maximal stimulation was observed using 10 microg/ml and 20 microg/ml of 3F10 mAb, respectively. The 3F10-induced stimulation of thymocytes proliferation in the presence of ConA, that was followed by increased production of interleukin-2 (IL-2), up-regulation of the expression of IL-2 receptor alpha (IL-2Ralpha) and was inhibited by anti-CD11a and anti-CD18 mAbs. Purified thymocytes did not respond by proliferation to 3F10 mAb, either alone or in combination with R73 mAb or ConA. Proliferation of these cells was achieved only in the presence of OX-6+ antigen-presenting cells (APC) and additional signals transmitted by TCR or ConA. These results suggest that Crry is involved in the LFA-1 dependent proliferation of thymocytes, a phenomenon that has not been recognized so far.  相似文献   
17.
The human peroxins PEX3 and PEX19 play a central role in peroxisomal membrane biogenesis. The membrane-anchored PEX3 serves as the receptor for cytosolic PEX19, which in turn recognizes newly synthesized peroxisomal membrane proteins. After delivering these proteins to the peroxisomal membrane, PEX19 is recycled to the cytosol. The molecular mechanisms underlying these processes are not well understood. Here, we report the crystal structure of the cytosolic domain of PEX3 in complex with a PEX19-derived peptide. PEX3 adopts a novel fold that is best described as a large helical bundle. A hydrophobic groove at the membrane-distal end of PEX3 engages the PEX19 peptide with nanomolar affinity. Mutagenesis experiments identify phenylalanine 29 in PEX19 as critical for this interaction. Because key PEX3 residues involved in complex formation are highly conserved across species, the observed binding mechanism is of general biological relevance.  相似文献   
18.
Despite continual membrane reorganization in the Golgi complex, the number of cisternae in a Golgi stack is a stable parameter. The cisternal number is conserved within any given cell line and also after Golgi reassembly, e.g. following brefeldin-A-induced disruption. However, the factors that determine the cisternal number in a single Golgi stack remain to be fully determined. We propose a simple mechanical model of the Golgi stack and present a theoretical analysis of different physical factors that may affect the number of cisternae in a Golgi stack. The model takes into account the Golgi membrane bending elasticity, which is related to the membrane curvature, and the adhesion, which holds the cisternae together. The analysis shows that the equilibrium configuration of the Golgi stack can be regarded as a balance between these two effects - the adhesion, which tends to increase the number of cisternae, is opposed by the membrane resistance to bending, which does not favor highly curved cisternal rims. The adhesion strength that is needed to hold together a typical stack is calculated. In addition, the model is used to analyze changes in the cisternal numbers as a controlled traffic wave enters a Golgi stack and increases the amount of the membrane in that stack.  相似文献   
19.
20.
We examine the effects of fructooligosaccharides (FOS) on the reduction in the incisor iron content in gastrectomized rat. Twenty-eight 5-wk-old male Sprague-Dawley rats were divided into two groups: sham operated (bSH) and gastrectomized (bGX). After 4 wk each group was divided into two subgroups according to the presence or absence of 7.5% FOS in the synthetic diet (SH, SH+FOS, GX, and GX+FOS). At 10 wk wafter surgery, the maxilla was prepared to examine the iron content of the incisor enamel surface at four points. These points corresponded to the iron content at 6,7,8, and 10 wk, respectively. Blood was collected to determine serum iron levels at 4 and 10 wk. The serum iron level significantly decreased at 4 and 10 wk the GX group. At 10 wk, the level in the GX+FOS group significantly increased but did not reaach that in the SH group. The iron content of the enamel surface time-dependently increased and no significant differences were seen between SH and GX+FOS at 8 and 10 wk. These results suggest that FOS consumption impaired the loss of enamel content following gastrectomy, and this effect preceded the effect on the serum iron level.  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