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   7369篇
  免费   722篇
  国内免费   391篇
  8482篇
  2023年   45篇
  2022年   108篇
  2021年   213篇
  2020年   178篇
  2019年   236篇
  2018年   251篇
  2017年   217篇
  2016年   294篇
  2015年   458篇
  2014年   455篇
  2013年   498篇
  2012年   656篇
  2011年   586篇
  2010年   393篇
  2009年   382篇
  2008年   474篇
  2007年   386篇
  2006年   329篇
  2005年   352篇
  2004年   375篇
  2003年   338篇
  2002年   298篇
  2001年   192篇
  2000年   141篇
  1999年   120篇
  1998年   70篇
  1997年   61篇
  1996年   43篇
  1995年   26篇
  1994年   33篇
  1993年   13篇
  1992年   29篇
  1991年   19篇
  1990年   17篇
  1989年   9篇
  1988年   16篇
  1987年   10篇
  1986年   8篇
  1985年   10篇
  1979年   11篇
  1977年   8篇
  1976年   10篇
  1975年   10篇
  1974年   10篇
  1973年   7篇
  1971年   8篇
  1970年   7篇
  1969年   11篇
  1968年   10篇
  1967年   7篇
排序方式: 共有8482条查询结果,搜索用时 0 毫秒
891.
Cyclin-dependent kinase (CDK) inhibitor p21WAF1/CIP1(-/-)-null mice have an increased incidence of tumor formation. Here, we demonstrate that p21WAF1/CIP1 is unstable in HeLa cells treated with siRNA duplexes that target PKCδ. PKCδ phosphorylates p21WAF1/CIP1 at a serine residue (146Ser) located in its C-terminal domain. In cells treated with 12-O-tetradecanoylphorbol 13-acetate, the levels of both p21WAF1/CIP1 and its 146Ser-phosphorylated form increased significantly. We also show that a substitution, resulting from a single nucleotide polymorphism (SNP) at 149Asp found in certain cancer patients, strongly compromises PKCδ-mediated phosphorylation at 146Ser and results in cells that are relatively resistant to TNFα-induced apoptosis. Thus, post-translational phosphorylation of p21WAF1/CIP1 is important from an apoptotic cell death, and may also have patho-physiological relevance for the development of human cancer.  相似文献   
892.
Lu Y  Ye L  Yu S  Zhang S  Xie Y  McKee MD  Li YC  Kong J  Eick JD  Dallas SL  Feng JQ 《Developmental biology》2007,303(1):191-201
Dentin matrix protein 1 (DMP1) is expressed in both pulp and odontoblast cells and deletion of the Dmp1 gene leads to defects in odontogenesis and mineralization. The goals of this study were to examine how DMP1 controls dentin mineralization and odontogenesis in vivo. Fluorochrome labeling of dentin in Dmp1-null mice showed a diffuse labeling pattern with a 3-fold reduction in dentin appositional rate compared to controls. Deletion of DMP1 was also associated with abnormalities in the dentinal tubule system and delayed formation of the third molar. Unlike the mineralization defect in Vitamin D receptor-null mice, the mineralization defect in Dmp1-null mice was not rescued by a high calcium and phosphate diet, suggesting a different effect of DMP1 on mineralization. Re-expression of Dmp1 in early and late odontoblasts under control of the Col1a1 promoter rescued the defects in mineralization as well as the defects in the dentinal tubules and third molar development. In contrast, re-expression of Dmp1 in mature odontoblasts, using the Dspp promoter, produced only a partial rescue of the mineralization defects. These data suggest that DMP1 is a key regulator of odontoblast differentiation, formation of the dentin tubular system and mineralization and its expression is required in both early and late odontoblasts for normal odontogenesis to proceed.  相似文献   
893.
蝇蛹金小蜂是铃木氏果蝇和黑腹果蝇的重要天敌,本研究以黑腹果蝇为寄主,测定了蝇蛹金小蜂云南种群的生长发育、繁殖及寿命。并在6个寄主密度梯度条件下研究了其寄生功能反应。结果显示蝇蛹金小蜂从卵到雌、雄成蜂的平均发育历期分别为16.10 d和14.67 d,雌蜂平均寿命为49.76 d,平均产子代数为93.28头/雌,子代雌性比为55.76%。在黑腹果蝇蛹为5、10、15、20、25和30头的密度梯度下,蝇蛹金小蜂的寄生功能反应符合Holling Ⅱ模型,其方程为Na=0.6261 No/(1+0.0632 No)。理论最高寄生量为N_a_(max)=9.0171,实际最高寄生量为7.00头(寄主密度为20头),蝇蛹金小蜂的寄生搜寻效应随寄主密度的增加而降低。综上结果,采自杨梅的蝇蛹金小蜂以黑腹果蝇作为寄主时具有较高繁殖力,较强的寄主适合度,是铃木氏果蝇和黑腹果蝇有效的生物防治作用因子。  相似文献   
894.
Objective: The objective of this study was to investigate the association among adiposity, insulin resistance, and inflammatory markers [high‐sensitivity C‐reactive protein (hs‐CRP), interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α] and adiponectin and to study the effects of exercise training on adiposity, insulin resistance, and inflammatory markers among obese male Korean adolescents. Research Methods and Procedures: Twenty‐six obese and 14 lean age‐matched male adolescents were studied. We divided the obese subjects into two groups: obese exercise group (N = 14) and obese control group (N = 12). The obese exercise group underwent 6 weeks of jump rope exercise training (40 min/d, 5 d/wk). Adiposity, insulin resistance, lipid profile, hs‐CRP, IL‐6, TNF‐α, and adiponectin were measured before and after the completion of exercise training. Results: The current study demonstrated higher insulin resistance, total cholesterol, LDL‐C levels, triglyceride, and inflammatory markers and lower adiponectin and HDL‐C in obese Korean male adolescents. Six weeks of increased physical activity improved body composition, insulin sensitivity, and adiponectin levels in obese Korean male adolescents without changes in TNF‐α, IL‐6, and hs‐CRP. Discussion: Obese Korean male adolescents showed reduced adiponectin levels and increased inflammatory cytokines. Six weeks of jump rope exercise improved triglyceride and insulin sensitivity and increased adiponectin levels.  相似文献   
895.
Odoroside A (OA) is an active ingredient extracted from the leaves of Nerium oleander Linn. (Apocynaceae). This study aims to examine the anticancer bioactivity of OA against CRC cells and to investigate the action mechanisms involved. As a result, OA can significantly inhibit cellular ability and induce apoptosis of CRC cells in a concentration‐dependent manner without any obvious cytotoxicity in normal colorectal epithelial cells. Then, quantitative proteomics combined with bioinformatics is adopted to investigate the alterations of proteins and signaling pathways in response to OA treatment. As suggested by the proteomic analysis, flow cytometry and Western blotting analyses validate that exposure of CRC cells to OA causes cell cycle arrest and apoptosis, accompanied with the activation of the ROS/p53 signaling pathway. This observation demonstrates that OA, as a natural product, can induce oxidative stress to suppress tumor cell growth, implicating a novel therapeutic agent against CRC without obvious side effects.  相似文献   
896.
Controlling electrochemical deposition of lithium sulfide (Li2S) is a major challenge in lithium–sulfur batteries as premature Li2S passivation leads to low sulfur utilization and low rate capability. In this work, the solvent's roles in controlling solid Li2S deposition are revealed, and quantitative solvent‐mediated Li2S growth models as guides to solvent selection are developed. It is shown that Li2S electrodeposition is controlled by electrode kinetics, Li2S solubility, and the diffusion of polysulfide/Li2S, which is dictated by solvent's donicity, polarity, and viscosity, respectively. These solvent‐controlled properties are essential factors pertaining to the sulfur utilization, energy efficiency and reversibility of lithium–sulfur batteries. It is further demonstrated that the solvent selection criteria developed in this study are effective in guiding the search for new and more effective electrolytes, providing effective screening and design criteria for computational and experimental electrolyte development for lithium–sulfur batteries.  相似文献   
897.
As an approach to understand how translation may affect protein folding, we analyzed structural and functional properties of the human estrogen receptor alpha synthesized by different eukaryotic translation systems. A minimum of three conformations of the receptor were detected using limited proteolysis and a sterol ligand-binding assay. The receptor in vitro translated in rabbit reticulocyte lysate was rapidly degraded by protease, produced major bands of about 34 kDa and showed a high affinity for estradiol. In a wheat germ translation system, the receptor was more slowly digested. Two soluble co-existing conformations were evident by different degradation patterns and estradiol binding. Our data show that differences in the translation machinery may result in alternative conformations of the receptor with distinct sterol binding properties. These studies suggest that components of the cellular translation machinery itself might influence the protein folding pathways and the relative abundance of different receptor conformers.  相似文献   
898.
Acylation reactions of naringin with palmitic acid were performed by a lipase after formation of highly concentrated homogeneous solutions. Their initial naringin concentration was 840–950 mM, which is 20–60 times greater than that in organic solvent media. The overall productivity of highly concentrated solutions was more than 15 times greater than those of organic phase media. The addition of DMSO (20–40%, w/w) to substrate mixtures lowered the melting temperature of a naringin–palmitic acid mixture (1:1 molar ratio) to about 40 °C. Reactions at 80 °C apparently followed Michaelis–Menten kinetics despite extremely high substrate concentrations. As the temperature increased from 60 °C to 80 °C, the apparent viscosity of the highly concentrated solution decreased remarkably from 4.31 Pa s to 0.063 Pa s. An activation energy of 7.65 kcal/mol obtained in a range of 60–75 °C suggests a diffusion-control. On the other hand, an activation energy of 17.09 kcal/mol in a range of 75–90 °C indicates a reaction-control. The highest product conversion yield of 33% (mol/mol) was obtained in a 10 h reaction at 80 °C. Addition of activated molecular sieves to the highly concentrated solution increased the product conversion yield by 7% (mol/mol), suggesting that the original equilibrium was disrupted by removing water and then a new equilibrium was reached.  相似文献   
899.
西藏拉萨地区三叠系诺利阶牙形石分带及其国际对比   总被引:7,自引:0,他引:7  
麦龙岗剖面位于西藏拉萨地区达孜县麦龙岗村 (N2 9°5 6′0 6″ ,E91°2 7′5 5″)。麦龙岗组中共发现牙形石 7属 :Epigondolella ,Hindeodella ,Priniodella ,Xaniognathodus,Lonchodina ,Metalonchodina和Enantiognathus属。其中Epigondolella属有 9种 ,包括 1新种和 1未定种 ,它们是E .primitia ,E .spiculata ,E .cf.spiculata ,E .tozeri,E .violinformissp .nov .,E .cf.triangularisuniformis,E .postera ,E .bidentata ,E .sp .。基于本次发现的化石材料 ,对西藏林周地区麦龙岗组进行新的牙形石带划分。自下而上划分为 :?Epigondolellaprimitia ,E .spiculata ,E .tozer i,E .postera和E .bidentata等带。与毛力等 (1987)、Orchard(1983,1991,1994 )和Krystyn(1977)的划分方案进行对比和讨论  相似文献   
900.
Based on highly selective and irreversible Hg2+-promoted desulfurization reaction, a new and simple phenanthroimidazole-type sensor was prepared and exhibited high selectivity towards Hg2+ ion over other metal ions, accompanied by transformation of a weakly fluorescent thioamide moiety (colorless) to a highly fluorescent amide one (blue), with a 136-fold increase in fluorescent intensity in aqueous solution with a pH span 2.57–9.12.  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