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   4859篇
  免费   452篇
  国内免费   366篇
  2024年   14篇
  2023年   74篇
  2022年   83篇
  2021年   250篇
  2020年   171篇
  2019年   255篇
  2018年   220篇
  2017年   139篇
  2016年   239篇
  2015年   359篇
  2014年   349篇
  2013年   364篇
  2012年   445篇
  2011年   383篇
  2010年   267篇
  2009年   246篇
  2008年   268篇
  2007年   247篇
  2006年   209篇
  2005年   147篇
  2004年   149篇
  2003年   135篇
  2002年   96篇
  2001年   87篇
  2000年   58篇
  1999年   75篇
  1998年   42篇
  1997年   35篇
  1996年   40篇
  1995年   28篇
  1994年   27篇
  1993年   32篇
  1992年   31篇
  1991年   27篇
  1990年   23篇
  1989年   11篇
  1988年   17篇
  1987年   7篇
  1986年   7篇
  1985年   11篇
  1984年   4篇
  1983年   2篇
  1982年   2篇
  1981年   1篇
  1976年   1篇
排序方式: 共有5677条查询结果,搜索用时 281 毫秒
971.
Sucrose non-fermenting-1-related protein kinase 1 (SnRK1) has been located at the heart of the control of metabolism and development in plants. The active SnRK1 form is usually a heterotrimeric complex. Subcellular localization and specific target of the SnRK1 kinase are regulated by specific beta subunits. In Arabidopsis , there are at least seven genes encoding beta subunits, of which the regulatory functions are not yet clear. Here, we tried to study the function of one beta subunit, AKINβ1. It showed that AKINβ1 expression was dramatically induced by ammonia nitrate but not potassium nitrate, and the investigation of AKINβ1 transgenic Arabidopsis and T-DNA insertion lines showed that AKINβ1 negatively regulated the activity of nitrate ruductase and was positively involved in sugar repression in early seedling development. Meanwhile AKINβ1 expression was reduced upon sugar treatment (including mannitol) and did not affect the activity of sucrose phosphate synthase. The results indicate that AKINβ1 is involved in the regulation of nitrogen metabolism and sugar signaling.  相似文献   
972.
Previous studies have revealed that Epstein-Barr virus (EBV) was closely associated with nasopharyngeal carcinoma (NPC). This study aimed to characterize the global pathways affected in the EBV-associated NPC. Combined with microdissection, gene expression profries in 22 NPCs and 10 non-tumor nasopharyngeal epithelial (NPE) tissue samples were analyzed. All NPC specimens served in the microarray analysis were positive for EBV, as judged by identification of the expression of EBV nuclear antigen 1 (EBNA1). Through gene set enrichment analysis (GSEA), we found that cell cycle pathway was the most disregulated pathway in NPC (P = 0.000, false discovery rate q-value = 0.007), which included some aberrant expressed components. We first found that overexpression of CDK4, cyclin D1, and Rb proteins, and loss of expression of proteins p16, p27, and p19 were statistically significant in NPC tissues compared with non-cancerous NPE (P〈 0.05) by real-time RT- PCR and tissue microarray. EBV-encoded small RNA-1 (EBER-1) hybridization signals in the NPC showed significant associations with the overexpression of Rb (P = 0.000), cyclin D1 (P = 0.000), CDK4 (P = 0.000), and the loss of expression of p16 proteins (P = 0.039). In the final logistic regression analysis model, EBER-1 and abnormal expression of p16, Rb, cyclin D1, and E2F6 were inde- pendent contributions to nasopharyngeal carcinogenesis. Through survival analysis, only cyclin D1 could predict the prognosis of NPC patients. These results suggested that cell cycle pathway was the most disregulated pathway in the EBV-associated NPC, and EBER-1 was closely associated with p16, CDK4, cyclin D1, and Rb. cyclin D1 could be the prognosis biomarker for NPC.  相似文献   
973.
目的:探讨一氧化氮供体药物硝酸甘油对对裸鼠胰腺癌皮下成瘤的抑制作用及对瘤体组织中低氧诱导因子1α(hypoxia induced factor 1α,HIF-1α),P糖蛋白(P-glucoprotein,P-gP)和谷胱甘肽S转移酶-π(Glutathione S-transferase pi,GST-π)的表达影响.方法:40只6-8周的18-22g的BALB/c裸鼠双侧腹股沟皮下注射胰腺癌PANC-1细胞成瘤,瘤体超过150mm3后随机分组,干预组用硝酸甘油帖剂干预,对照组贴安慰剂,并分别绘制生长曲线.采用免疫组织化学方法检测成瘤裸鼠中瘤体组织中HIF-1α、P-gP和GST-π的表达.结果:32例裸鼠成瘤,成瘤率80%,干预28天后,干预组和对照组的瘤体大小分别为1550.4±148.6mm3和750.6±71.2mm3.16只对照组瘤体组织中HIF-1α阳性表达12例(75%),P-gp阳性表达10例(62.5%),GsT-π阳性表达8例(50%).在16例干预组裸鼠瘤体组织中HIF-1α、P-gP、GST-π阳性表达分别是11例(68.8%),8例(50%),7例(43.8%).结论:特定剂量硝酸甘油对裸鼠皮下成瘤有明显抑制作用,且对HIF-1α及P-gp、GsT-π的表达也有一定的抑制作用.  相似文献   
974.
1998年,Thomson等成功分离出了人类胚胎干细胞(embryonic stem cell,ES)系为研究再生医学和人类早期发育开辟了一个新领域.通过转染人类ES细胞进行遗传操作(genetic manipulation)可以帮助我们更好地理解人类Es细胞的生物学特性,同时为研究人类ES细胞在细胞及基因治疗中潜在的治疗用途提供了基础.本文综述了人类ES细胞外源基因转染方法及其应用的进展.  相似文献   
975.
976.

Background  

The Twin-arginine translocation (Tat) system serves to translocate folded proteins, including periplasmic enzymes that bind redox cofactors in bacteria. The Tat system is also a determinant of virulence in some pathogenic bacteria, related to pleiotropic effects including growth, motility, and the secretion of some virulent factors. The contribution of the Tat pathway to Vibrio cholerae has not been explored. Here we investigated the functionality of the Tat system in V. cholerae, the etiologic agent of cholera.  相似文献   
977.

Background  

The phylogeny of Cetacea (whales) is not fully resolved with substantial support. The ambiguous and conflicting results of multiple phylogenetic studies may be the result of the use of too little data, phylogenetic methods that do not adequately capture the complex nature of DNA evolution, or both. In addition, there is also evidence that the generic taxonomy of Delphinidae (dolphins) underestimates its diversity. To remedy these problems, we sequenced the complete mitochondrial genomes of seven dolphins and analyzed these data with partitioned Bayesian analyses. Moreover, we incorporate a newly-developed "relaxed" molecular clock to model heterogenous rates of evolution among cetacean lineages.  相似文献   
978.

Background  

Dorsal root ganglion (DRG) neurons are primary sensory neurons that conduct neuronal impulses related to pain, touch and temperature senses. Plasma membrane (PM) of DRG cells plays important roles in their functions. PM proteins are main performers of the functions. However, mainly due to the very low amount of DRG that leads to the difficulties in PM sample collection, few proteomic analyses on the PM have been reported and it is a subject that demands further investigation.  相似文献   
979.
It is expected that the CO2 concentration of the Earth’s atmosphere will reach 600–1000 ppm by the end of the 21st century. Therefore, in this study, we evaluated the effects of elevated CO2 concentrations on the development of rain-fed spring wheat in an attempt to identify a practical pathway to increase crop production. To accomplish this, a field experiment was conducted at Guyuan Experimental Station in a semiarid region of China during 2005–2007. During this experiment, the CO2 concentration was increased to 40.0 ppm and supplemental irrigation and nitrogenous fertilizer (N fertilizer) were applied. The experimental results showed that the elevated CO2 concentration significantly improved the thousand-grain weight and the grain number per spike. Furthermore, supplemental irrigation and N fertilizer application during the elongation and booting stage of rain-fed spring wheat in conjunction with an elevated CO2 concentration improved the water use efficiency (WUE), nitrogen use efficiency (NUE), thousand-grain weight, and the yield by 14.6%, 39.6%, 9.3%, and 14.7%, respectively, when compared to groups subjected to the same treatment but not grown under elevated CO2 concentrations. Furthermore, the spring wheat yield was improved by 81.8% in response to an elevated CO2 concentration, 60 mm of supplemental irrigation and applied N fertilizer (37.5 g m?2 NH4NO3). However, the presence of an elevated CO2 concentration without supplemental irrigation and N fertilizer only resulted in an increase in the wheat yield of 7.8%. Consequently, the combination of elevated CO2 concentration, supplemental irrigation and N fertilizer application played an important role in the improvement of WUE, NUE, thousand-grain weight, and grain yield of rain-fed spring wheat in this region.  相似文献   
980.
A clinically-related animal model of Parkinson''s disease (PD) may enable the elucidation of the etiology of the disease and assist the development of medications. However, none of the current neurotoxin-based models recapitulates the main clinical features of the disease or the pathological hallmarks, such as dopamine (DA) neuron specificity of degeneration and Lewy body formation, which limits the use of these models in PD research. To overcome these limitations, we developed a rat model by stereotaxically (ST) infusing small doses of the mitochondrial complex-I inhibitor, rotenone, into two brain sites: the right ventral tegmental area and the substantia nigra. Four weeks after ST rotenone administration, tyrosine hydroxylase (TH) immunoreactivity in the infusion side decreased by 43.7%, in contrast to a 75.8% decrease observed in rats treated systemically with rotenone (SYS). The rotenone infusion also reduced the DA content, the glutathione and superoxide dismutase activities, and induced alpha-synuclein expression, when compared to the contralateral side. This ST model displays neither peripheral toxicity or mortality and has a high success rate. This rotenone-based ST model thus recapitulates the slow and specific loss of DA neurons and better mimics the clinical features of idiopathic PD, representing a reliable and more clinically-related model for PD research.  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