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   1841篇
  免费   136篇
  国内免费   200篇
  2024年   3篇
  2023年   35篇
  2022年   71篇
  2021年   130篇
  2020年   98篇
  2019年   103篇
  2018年   102篇
  2017年   81篇
  2016年   97篇
  2015年   146篇
  2014年   136篇
  2013年   163篇
  2012年   177篇
  2011年   149篇
  2010年   80篇
  2009年   66篇
  2008年   78篇
  2007年   74篇
  2006年   54篇
  2005年   33篇
  2004年   31篇
  2003年   30篇
  2002年   35篇
  2001年   17篇
  2000年   20篇
  1999年   14篇
  1998年   14篇
  1997年   18篇
  1996年   5篇
  1995年   6篇
  1994年   5篇
  1993年   11篇
  1992年   6篇
  1991年   4篇
  1990年   7篇
  1989年   4篇
  1988年   4篇
  1987年   10篇
  1986年   3篇
  1985年   5篇
  1984年   5篇
  1983年   3篇
  1976年   4篇
  1975年   3篇
  1973年   10篇
  1972年   2篇
  1970年   2篇
  1968年   3篇
  1967年   3篇
  1966年   8篇
排序方式: 共有2177条查询结果,搜索用时 15 毫秒
31.
32.
Atherosclerosis is one of the most common and crucial heart diseases involving the heart and brain. At present, atherosclerosis and its major complications comprise the leading causes of death worldwide. Our purpose was to identify the role of ciRS‐7 in atherosclerosis. Tubulogenesis of HMEC‐1 cell was evaluated utilizing tube formation assay. Cell Counting Kit‐8 assay and flow cytometry were utilized to test viability and apoptosis. Migration assay was utilized to determine the migration capacity of experimental cells. Western blot was applied to examine apoptosis and tube formation‐associated protein expression. In addition, the above experiments were repeated when silencing ciRS‐7, overexpressing ciRS‐7, and upregulating miR‐26a‐5p. HMEC‐1 cells formed tube‐like structures over time. Silencing ciRS‐7 suppressed viability, migration, and tube formation but promoted apoptosis. Oppositely, overexpressing ciRS‐7 reversed the effect in HMEC‐1 cells. miR‐26a‐5p expression was elevated by silencing ciRS‐7 and reduced by overexpressing ciRS‐7. Moreover, overexpressing ciRS‐7 facilitated viability, migration, and tube formation via upregulating miR‐26a‐5p. Conclusively, overexpressing ciRS‐7 mobilized phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway and suppressed c‐Jun N‐terminal kinase (JNK)/p38 pathway. ciRS‐7 exerted influence on apoptosis, viability, migration, and tube formation through mediating PI3K/AKT and JNK/p38 pathways by miR‐26a‐5p downregulation in HMEC‐1 cells.  相似文献   
33.
Zhang  Ziyi  Tang  Shengjie  Gui  Weiwei  Lin  Xihua  Zheng  Fenping  Wu  Fang  Li  Hong 《Journal of physiology and biochemistry》2020,76(2):317-328

Podocyte injury plays a key role in the occurrence and development of kidney diseases. Decreased autophagic activity in podocyte is closely related to its injury and the occurrence of proteinuria. Liver X receptors (LXRs), as metabolic nuclear receptors, participate in multiple pathophysiological processes and express in several tissues, including podocytes. Although the functional roles of LXRs in the liver, adipose tissue and intestine are well established; however, the effect of LXRs on podocytes function remains unclear. In this study, we used mouse podocytes cell line to investigate the effects of LXR activation on podocytes autophagy level and related signaling pathway by performing Western blotting, RT-PCR, GFP-mRFP-LC3 transfection, and immunofluorescence staining. Then, we tested this effect in STZ-induced diabetic mice. Transmission electron microscopy and immunohistochemistry were employed to explore the effects of LXR activation on podocytes function and autophagic activity. We found that LXR activation could inhibit autophagic flux through blocking the formation of autophagosome in podocytes in vitro which was possibly achieved by affecting AMPK, mTOR, and SIRT1 signaling pathways. Furthermore, LXR activation in vivo induced autophagy suppression in glomeruli, leading to aggravated podocyte injury. In summary, our findings indicated that activation of LXRs induced autophagy suppression, which in turn contributed to the podocyte injury.

  相似文献   
34.
Cardamonin (CD), a naturally occurring chalcone isolated from large black cardamom, was previously reported to suppress the proliferation of breast cancer cells. However, its precise molecular anti‐tumor mechanisms have not been well elucidated. In this study, we found that CD markedly inhibited the proliferation of MDA‐MB 231 and MCF‐7 breast cancer cells through the induction of G2/M arrest and apoptosis. Reactive oxygen species (ROS) plays a pivotal role in the inhibition of CD‐induced cell proliferation. Treatment with N‐acetyl‐cysteine (NAC), an ROS scavenger, blocked CD‐induced G2/M arrest and apoptosis in this study. Quenching of ROS by overexpression of catalase also blocked CD‐induced cell cycle arrest and apoptosis. We showed that CD enhanced the expression and nuclear translocation of Forkhead box O3 (FOXO3a) via upstream c‐Jun N‐terminal kinase, inducing the expression of FOXO3a and its target genes, including p21, p27, and Bim. This process led to the reduction of cyclin D1 and enhancement of activated caspase‐3 expression. The addition of NAC markedly reversed these effects, knockdown of FOXO3a using small interfering RNA also decreased CD‐induced G2/M arrest and apoptosis. In vivo, CD efficiently suppressed the growth of MDA‐MB 231 breast cancer xenograft tumors. Taken together, our data provide a molecular mechanistic rationale for CD‐induced cell cycle arrest and apoptosis in breast cancer cells.  相似文献   
35.
36.
为研究三峡水库消落带优势植物的养分利用特征及其对生境的适应策略,选择消落带分布最多的4种草本植物为研究对象,分析了植物根、茎、叶的碳(C)、氮(N)、磷(P)、钾(K)含量和化学计量比特征。结果表明:(1)相比陆地系统和自然湿地系统,消落带植物具有较低的C含量和较高的N、P、K含量,C/N、C/P、C/K均较低,表明植物具有低固碳和高养分积累、低养分利用效率和高生长速率的特征;(2)4种植物的养分含量和计量比存在一定差异,其中狗牙根具有较低的N、P、K含量和较高的C/N、C/P、C/K,且变异系数均低于其他3种植物,其低养分需求、高养分利用效率以及较强的内稳性可能是其在库区分布最广的重要机制;(3)4种植物在不同器官的养分分配策略相似,均表现为叶片C含量低于根和茎,而N、P、K含量则显著高于根、茎;同时,与根、茎相比,叶片C/N、C/P、C/K较低,N/P、N/K较高,且在不同生境条件下变异系数较小,表现出相对较高的稳定性;(4)落消带植物的养分含量及计量比从全库区上游至下游的空间变异性较强,其中N、C/N、N/P变异性较大,而C、P、K变异性较小,表明植物N含量受生境变化的影响较大,加之消落带不同植物生长均受到严格的N限制,因此N供给可能是影响消落带生态系统结构的重要因子。三峡库区消落带植物生态化学计量特征具有明显的变异性和特殊性,是植物群落演替及生态系统功能变化的重要驱动因素。  相似文献   
37.
The ecosystem and Pleistocene glaciations play important roles in population demography. The freshwater gudgeon, Gobiobotia filifer, is an endemic benthic fish in the Yangtze River and is a good model for ecological and evolutionary studies. This study aimed to decode the population structure of G. filifer in the Yangtze River and reveal whether divergence occurred before or after population radiation. A total of 292 specimens from eight locations in the upper and middle reaches of the Yangtze River were collected from 2014 to 2016 and analyzed via mitochondrial DNA Cyt b gene sequencing. A moderately high level of genetic diversity was found without structures among the population. However, phylogenetic and network topology showed two distinct haplotype groups, and each group contained a similar proportion of individuals from all sampled sites. This suggested the existence of two genetically divergent source populations in G. filifer. We deduced that a secondary contact of distinct glacial refugia was the main factor creating sympatric populations of G. filifer, and climate improvement promoted population expansion and colonization.  相似文献   
38.
为拓宽小麦矮秆遗传资源,利用γ射线辐照济麦22获得了一个赤霉素不敏感型矮秆突变体jm22d。株高相关性状调查结果及茎秆细胞学试验显示,jm22d株高为53±1.8 cm,比野生型(WT)低约20 cm。jm22d整株茎秆共有4节,比WT少一节且各节间长度显著小于WT。与WT相比,jm22d茎秆细胞长度缩短。赤霉素含量测定发现,jm22d叶片中赤霉素含量高于WT,而茎秆中赤霉素含量低于WT(P<0.01),因此,jm22d株高降低与赤霉素转运途径出现异常有关。为了深入研究jm22d对赤霉素的响应机理,对jm22d和WT幼苗进行赤霉素处理,分别收取处理0(D0)、1(D1)和3 d(D3)的样品进行转录组学分析。结果表明,与WT相比,在jm22d中共筛选到696个上调和1 067个下调的表达基因,其中62个和349个基因在3个时间点分别表现为上调和下调表达。叶绿素含量测定表明,jm22d中叶绿素含量随赤霉素处理时间的延长而降低,聚类分析结果表明,差异表达基因主要富集在光合作用-天线蛋白(photosynthesis-antenna proteins,ko00196)、卟啉和叶绿素代谢(porphyrin and chlorophyll metabolism,ko00860)、亚油酸新陈代谢(linoleic acid metabolism,ko00591)等通路,因此赤霉素处理对jm22d体内叶绿素含量的积累具有抑制作用。通过KEGG分析在植物激素信号转导途径中挖掘到5个差异表达基因(TraesCS2B01G582300、TraesCS2B01G600800、TraesCS2B01G556600、TraesCS2B01G630000和TraesCS6B01G439600)参与生长素、细胞分裂素等激素代谢途径,这些基因在jm22d中显著下调,这可能是jm22d矮化的重要原因。研究结果为矮秆突变体矮化机制的解析提供了重要参考。  相似文献   
39.
[背景] 人体能量稳态失衡表现为体重过轻、超重和肥胖,肠道菌群与人体能量稳态的维持有关,但不同身体质量指数(Body Mass Index,BMI)人群的肠道菌群特征仍需进一步探究。[目的] 基于美国肠道计划公开数据库,解析4类BMI人群肠道菌群的特征,并探究4类BMI人群肠道菌群共存网络特征及差异,为基于肠道菌群来干预肥胖及体重过轻等不健康状态提供新的理论依据。[方法] 从美国肠道计划数据集中筛选具有BMI信息的肠道菌群样本,并根据世界卫生组织规定的BMI划分标准将筛选后的样本分为4类:体重过轻(BMI<18.5 kg/m2),正常体重(18.5 kg/m22),超重(25 kg/m22),肥胖(BMI>30 kg/m2);通过计算和比较肠道菌群的α多样性和β多样性探究4类BMI人群肠道菌群的整体结构特征及差异;通过多元线性回归模型对不同BMI分类与肠道菌群进行相关性分析,并且将地域、年龄、性别因素作为混杂因素加入到模型中进行校正;采用SparCC分别计算4类BMI人群肠道菌群中菌属相关性,并分别构建肠道菌群共存网络。[结果] 经过Wilcoxon秩和检验,发现体重过轻、超重、肥胖人群的肠道菌群α多样性都显著低于正常体重人群;β多样性分析结果表明4类BMI人群肠道菌群的整体结构存在显著差异;4类BMI人群肠道中厚壁菌门(Firmicutes)和拟杆菌门(Bacteroidetes)的相对含量无显著差异;通过MaAsLin分析,并且将地域、年龄、性别因素作为混杂因素加入到模型中进行校正,共得到49个与BMI类型显著相关的物种;4类BMI人群肠道菌群共存网络的拓扑结构具有一定差异,体重过轻和正常体重人群肠道菌群共存网络的复杂度较高,超重和肥胖人群肠道菌群共存网络的复杂度较低。[结论] 4类BMI人群肠道菌群的多样性、整体结构和共存网络间均存在差异。  相似文献   
40.
Yan  Yan  Zhao  Sihan  Ding  Zehong  Tie  Weiwei  Hu  Wei 《Plant Molecular Biology Reporter》2021,39(3):607-616
Plant Molecular Biology Reporter - Cassava is an important starchy and food crop; however, the commercial value of cassava is seriously constrained by postharvest physiological deterioration (PPD)....  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