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   6184篇
  免费   405篇
  国内免费   430篇
  7019篇
  2024年   11篇
  2023年   68篇
  2022年   188篇
  2021年   312篇
  2020年   193篇
  2019年   252篇
  2018年   231篇
  2017年   189篇
  2016年   253篇
  2015年   385篇
  2014年   445篇
  2013年   470篇
  2012年   543篇
  2011年   518篇
  2010年   340篇
  2009年   279篇
  2008年   331篇
  2007年   289篇
  2006年   259篇
  2005年   226篇
  2004年   191篇
  2003年   148篇
  2002年   131篇
  2001年   98篇
  2000年   80篇
  1999年   85篇
  1998年   43篇
  1997年   58篇
  1996年   58篇
  1995年   45篇
  1994年   32篇
  1993年   35篇
  1992年   48篇
  1991年   42篇
  1990年   28篇
  1989年   21篇
  1988年   12篇
  1987年   25篇
  1986年   16篇
  1985年   15篇
  1984年   1篇
  1983年   6篇
  1982年   5篇
  1981年   3篇
  1980年   4篇
  1977年   2篇
  1974年   1篇
  1973年   2篇
  1968年   1篇
  1967年   1篇
排序方式: 共有7019条查询结果,搜索用时 0 毫秒
991.
This paper investigated the concentrations of Pb in foods and the potential health risk from Pb exposure via surveys and a literature review. It was shown that the mean Pb concentration in different food groups was in the following decreasing order: marine products > meat > egg > vegetable > cereal > bean> dairy > fruit. More precisely, on average the weekly Pb intake (mg kg?1 bw week?1) for men, women, 2–3-year-old children, and 4–17-year-old children was 0.0055, 0.0059, 0.0145, and 0.0091, respectively. We used both deterministic and probabilistic methods to estimate the target hazard quotients (THQs) by comparing the dietary Pb intake estimation with respect to the provisional tolerable weekly intake (PTWI). The result showed that THQ values were lower than 1 in most cases, except the 97.5th percentile THQ values for 2–3-year-old children, and the probability of greater dietary Pb exposure than the tolerant weekly intake (THQ > 1) were 0.2%, 0.6%, 3.7%, and 1.2% for adult men, women, 2–3-year-old children, and 4–17-year-old children, respectively, indicating a low health risk for Chinese consumers. Among all groups, children, especially 2–3-year-old children were the most sensitive sub-population with regard to Pb exposure. Finally, it still appeared necessary to continue undertaking efforts to reduce exposure to Pb.  相似文献   
992.

Background

Gene therapy has gained an increasing interest in its anti-tumor efficiency. However, numerous efforts are required to promote them to clinics. In this study, a novel and efficient delivery platform based on bacterial magnetosomes (BMs) were developed, and the efficiency of BMs in delivering small interfering ribonucleic acid (siRNA) as well as antiproliferative effects in vitro were investigated.

Results

Initially, we optimized the nitrogen/phosphate ratio and the BMs/siRNA mass ratio as 20 and 1:2, respectively, to prepare the BMs–PEI–siRNA composites. Furthermore, the prepared nanoconjugates were systematically characterized. The dynamic light scattering measurements indicated that the particle size and the zeta potential of BMs–PEI–siRNA are 196.5 nm and 49.5 ± 3.77 mV, respectively, which are optimum for cell internalization. Moreover, the confocal laser scanning microscope observations showed that these composites were at a proximity to the nucleus and led to an effective silencing effect. BMs–PEI–siRNA composites efficiently inhibited the growth of HeLa cells in a dose-as well as time-dependent manner. Eventually, a dual stain assay using acridine orange/ethidium bromide, revealed that these nanocomposites induced late apoptosis in cancer cells.

Conclusions

A novel and efficient gene delivery system based on BMs was successfully produced for cancer therapy, and these innovative carriers will potentially find widespread applications in the pharmaceutical field.
  相似文献   
993.
994.
995.
A variant within the gene locus encoding PTPN22 (protein tyrosine phosphatase, non-receptor type 22) emerged as an important risk factor for auto-inflammatory disorders, including rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes, but at the same time protects from Crohn disease, one of the 2 main forms of inflammatory bowel diseases. We have previously shown that loss of PTPN22 results in decreased NLRP3 (NLR family pyrin domain containing 3) activation and that this effect is mediated via enhanced NLRP3 phosphorylation. However, it is unclear how phosphorylation of NLRP3 mediates its inhibition. Here, we demonstrate that loss of macroautophagy/autophagy abrogates the inhibitory effect on NLRP3 activation observed upon loss of PTPN22. Phosphorylated, but not nonphosphorylated NLRP3 is found in autophagosomes, indicating that NLRP3 phosphorylation mediates its inactivation via promoting sequestration into phagophores, the precursors to autophagosomes. This finding shows that autophagy and NLRP3 inflammasome activation are connected, and that PTPN22 plays a key role in the regulation of those 2 pathways. Given its role in inflammatory disorders, PTPN22 might be an attractive therapeutic target, and understanding the cellular mechanisms modulated by PTPN22 is of crucial importance.  相似文献   
996.
997.

Aims

The aim of this study was to examine the effect of plant species differing in functional and phylogenetic traits on the decomposition processes of leaf litter in a grassland of Japanese pampas grass (Miscanthus sinensis) and adjacent forests of Japanese red pine (Pinus densiflora) and Japanese oak (Quercus crispula), representing sequential stages of secondary succession.

Methods

The litterbag experiments were carried out for 3 years in a temperate region of central Japan.

Results

The decomposition constant (Olson’s k) was 0.49, 0.39, and 0.56/year for grass, pine, and oak, respectively. Nitrogen mass decreased in grass leaf litter during decomposition, whereas the absolute amount of nitrogen increased in leaf litter of pine and oak during the first year. Holocellulose in grass leaf litter decomposed selectively over acid-unhydrolyzable residues more markedly than in leaf litter of pine and oak. 13C nuclear magnetic resonance analysis also revealed a decrease in the relative area of O-alkyl-C in grass.

Conclusions

The different decomposition among the three litter species implied that the secondary succession from grassland to pine forest and from pine to oak forests could decrease and increase, respectively, the rate of accumulation and turnover of organic materials and N in soils.  相似文献   
998.
In conditioned taste aversion (CTA) training performed on the pond snail Lymnaea stagnalis, a stimulus (the conditional stimulus, CS; e.g., sucrose) that elicits a feeding response is paired with an aversive stimulus (the unconditional stimulus, US) that elicits the whole-body withdrawal response and inhibits feeding. After CTA training and memory formation, the CS no longer elicits feeding. We hypothesize that one reason for this result is that after CTA training the CS now elicits a fear response. Consistent with this hypothesis, we predict the CS will cause (1) the heart to skip a beat and (2) a significant change in the heart rate. Such changes are seen in mammalian preparations exposed to fearful stimuli. We found that in snails exhibiting long-term memory for one-trial CTA (i.e., good learners) the CS significantly increased the probability of a skipped heartbeat, but did not significantly change the heart rate. The probability of a skipped heartbeat was unaltered in control snails given backward conditioning (US followed by CS) or in snails that did not acquire associative learning (i.e., poor learners) after the one-trial CTA training. These results suggest that as a consequence of acquiring CTA, the CS evokes conditioned fear in the conditioned snails, as evidenced by a change in the nervous system control of cardiac activity.  相似文献   
999.
Jiang QT  Liu T  Ma J  Wei YM  Lu ZX  Lan XJ  Dai SF  Zheng YL 《Genetica》2011,139(10):1283-1292
The pre-mRNA processing (Prp1) gene encodes a spliceosomal protein. It was firstly identified in fission yeast and plays a regular role during spliceosome activation and cell cycle. Plant Prp1 genes have only been identified from rice, Sorghum and Arabidopsis thaliana. In this study, we reported the identification and isolation of a novel Prp1 gene from barley, and further explored its expressional pattern by using real-time quantitative RT-PCR, promoter prediction and analysis of microarray data. The putative barley Prp1 protein has a similar primary structure features to those of other known Prp1 protein in this family. The results of amino acid comparison indicated that Prp1 protein of barley and other plant species has a highly conserved 3′ termnal region while their 5′ sequences greatly varied. The results of expressional analysis revealed that the expression level of barley Prp1 gene is always stable in different vegetative tissues, except it is up-regulated at the mid- and late stages of seed development or under the condition of cold stress. This kind of expressional pattern for barley Prp1 is also supported by our results of comparison of microarray data from barley, rice and Arabidopsis. For the molecular mechanism of its expressional pattern, we conclude that the expression of Prp1 gene may be up-regulated by the increase of pre-mRNAs and not be constitutive or ubiquitous.  相似文献   
1000.
A class of anti-virulence compounds, the salicylidene acylhydrazides, has been widely reported to block the function of the type three secretion system of several Gram-negative pathogens by a previously unknown mechanism. In this work we provide the first identification of bacterial proteins that are targeted by this group of compounds. We provide evidence that their mode of action is likely to result from a synergistic effect arising from a perturbation of the function of several conserved proteins. We also examine the contribution of selected target proteins to the pathogenicity of Yersinia pseudotuberculosis and to expression of virulence genes in Escherichia coli O157.  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