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   2829篇
  免费   209篇
  国内免费   206篇
  2024年   4篇
  2023年   42篇
  2022年   99篇
  2021年   192篇
  2020年   109篇
  2019年   130篇
  2018年   119篇
  2017年   115篇
  2016年   156篇
  2015年   197篇
  2014年   210篇
  2013年   246篇
  2012年   272篇
  2011年   245篇
  2010年   147篇
  2009年   119篇
  2008年   147篇
  2007年   113篇
  2006年   88篇
  2005年   69篇
  2004年   63篇
  2003年   48篇
  2002年   42篇
  2001年   32篇
  2000年   24篇
  1999年   29篇
  1998年   17篇
  1997年   20篇
  1996年   23篇
  1995年   12篇
  1994年   19篇
  1993年   9篇
  1992年   11篇
  1991年   11篇
  1990年   11篇
  1989年   8篇
  1988年   6篇
  1987年   3篇
  1986年   4篇
  1985年   6篇
  1984年   2篇
  1983年   3篇
  1981年   2篇
  1979年   3篇
  1978年   2篇
  1973年   2篇
  1971年   2篇
  1968年   3篇
  1955年   2篇
  1954年   1篇
排序方式: 共有3244条查询结果,搜索用时 15 毫秒
121.
本文对2021年发表的膜翅目昆虫新分类单元进行了梳理和总结。结合数据库检索, 基于标本记录, 全球膜翅目学者于2021年发表该目新分类单元的期刊论文355篇, 新增分类单元条目共1,152条, 隶属于21总科66科416属, 包括5新科4新亚科83新属3新亚属1,054新种和3新亚种。现生类群相关期刊论文309篇, 新增分类单元条目980条, 隶属于18总科52科332属, 包括2新科26新属3新亚属946新种和3新亚种。绝灭类群相关期刊论文46篇, 新增分类单元条目172条, 隶属于14总科27科86属, 包括3新科4新亚科57新属和108新种。2021年中国膜翅目新增分类单元的相关期刊论文83篇, 新增分类单元条目235条, 隶属于17总科34科91属, 包括3新属(绝灭类群1新属)和232新种(绝灭类群2新种); 现生类群中新增的2属分别记录自台湾和浙江, 新种数量排前五位的省级行政单位有云南(54个)、浙江(42个)、福建(18个)、西藏(18个)和新疆(16个)。在全球现生、绝灭和中国现生膜翅目总科新物种数量的对比中, 姬蜂总科新种数量最多, 分别约占全球现生、绝灭和中国现生膜翅目新种总数的32.5% (307个/946个)、19.4% (21个/108个)和37.0% (85个/230个)。有关现生膜翅目新种发表情况, 在洲级地理单元中, 亚洲发表新种数量最多, 约占56.9% (538个); 在洲级地理亚单元中, 东亚发表新种数量最多, 约占28.6% (271个); 在国家和地区行政单元中, 中国发表新种数量最多, 约占24.3% (230个)。在76种期刊的355篇论文中, 有348篇英文论文、4篇中文论文和3篇法语论文。这些结果表明, 中国膜翅目分类在全球膜翅目分类中发挥着十分重要的作用。  相似文献   
122.
The brain-derived neurotrophic factor (BDNF) was first recognized for its roles in the peripheral and central nervous systems, and its complex functions on mammalian organs have been extended constantly. However, to date, little is known about its effects on the male reproductive system, including the steroidogenesis of mammals. The purpose of this study was to elucidate the effects of BDNF on testosterone generation of Leydig cells and the underlying mechanisms. We found that BDNF-induced proliferation of TM3 Leydig cells via upregulation of proliferating cell nuclear antigen ( Pcna) and promoted testosterone generation as a result of upregulation of steroidogenic acute regulatory protein ( Star), 3b-hydroxysteroid dehydrogenase ( Hsd3b1), and cytochrome P450 side-chain cleavage enzyme ( Cyp11a1) both in primary Leydig cells and TM3 Leydig cells, which were all attenuated in Bdnf knockdown TM3 Leydig cells. Furthermore, the possible mechanism of testosterone synthesis was explored in TM3 Leydig cells. The results showed that BDNF enhanced extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation, and the effect was disrupted by Bdnf deletion. Moreover, PD98059, a potent selective inhibitor of ERK1/2 activation, compromised BDNF-induced testosterone generation and upregulation of Star, Hsd3b1, and Cyp11a1. The Bdnf knockdown assay, on the other hand, indicated the autocrine effect of BDNF on steroidogenesis in TM3 Leydig cells. On the basis of these results, we concluded that BDNF, acting as an autocrine factor, induced testosterone generation as a result of the upregulation of Star, Hsd3b1, and Cyp11a1 via stimulation of the ERK1/2 pathway.  相似文献   
123.
A pyrogen test is crucial for evaluating the safety of drugs and medical equipment, especially those involved in injections. As existing pyrogen tests, including the rabbit pyrogen test, the limulus amoebocyte lysate (LAL) test and the monocyte activation test have limitations, development of new models for pyrogen testing is necessary. Here we develop a sensitive cell model for pyrogen test based on the lipopolysaccharides (LPS) signal pathway. TLR4, MD2, and CD14 play key roles in the LPS-mediated pyrogen reaction. We established a new TLR4/MD2/CD14-specific overexpressing knock-in cell model using the CRISPR/CAS9 technology and homologous recombination to detect LPS. Stimulation of our TLR4/CD14/MD2 knock-in cell line model with LPS leads to the release of the cytokines IL-6 and TNF-alpha, with a detection limit of 0.005 EU/ml, which is greatly lower than the lower limit of 0.015 EU/ml detected by the Tachypleus amebocyte lysate (TAL) assay.  相似文献   
124.
Liu  Hong  Yang  Jie  Wang  Kai  Niu  Tengfei  Huang  Dongya 《Neurochemical research》2019,44(5):1065-1078
Neurochemical Research - Mounting evidences have demonstrated that diet-induced obesity is associated with cognition impairment via increasing oxidative stress and inflammation in the brain....  相似文献   
125.
Previous studies found that the activity of Sortase A, a bacterial surface protein from Staphylococcus aureus, was inhibited by curcumin and its analogues. To explore this inhibitory mechanism, Sortase A and its inhibitors in complex systems were studied by molecular docking, molecular modelling, binding energy decomposition calculation and steered molecular dynamics simulations. Energy decomposition analysis indicated that PRO-163, LEU-169, GLN-172, ILE-182 and ILE-199 are key residues in Sortase A-inhibitor complexes. Furthermore, interactions between the methoxyl group on the benzene ring in the conjugated molecule (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and VAL-168, LEU-169 and GLN-172 induce the inhibitory activity based on the energy decomposition and distance analyses between the whole residues and inhibitors. However, because of its coiled structure, the non-conjugated molecule, tetrahydrocurcumin, with key residues in the binding sites of Sortase A, interacted weakly with SrtA, leading to the loss of inhibitory activity. Based on these results, the methoxyl group on the benzene ring in the conjugated molecule largely influenced the inhibitory activity of the Sortase A inhibitors.  相似文献   
126.
127.
Transient receptor potential vanilloid 3 (TRPV3), robustly expressed in the skin, is a nonselective calcium-permeable cation channel activated by warm temperature, voltage, and certain chemicals. Natural monoterpenoid carvacrol from plant oregano is a known skin sensitizer or allergen that specifically activates TRPV3 channel. However, how carvacrol activates TRPV3 mechanistically remains to be understood. Here, we describe the molecular determinants for chemical activation of TRPV3 by the agonist carvacrol. Patch clamp recordings reveal that carvacrol activates TRPV3 in a concentration-dependent manner, with an EC50 of 0.2 mM, by increasing the probability of single-channel open conformation. Molecular docking of carvacrol into cryo-EM structure of TRPV3 combined with site-directed mutagenesis further identified a unique binding pocket formed by the channel S2-S3 linker important for mediating this interaction. Within the binding pocket consisting of four residues (Ile505, Leu508, Arg509, and Asp512), we report that Leu508 is the most critical residue for the activation of TRPV3 by carvacrol, but not 2-APB, a widely used nonspecific agonist and TRP channel modulator. Our findings demonstrate a direct binding of carvacrol to TRPV3 by targeting the channel S2-S3 linker that serves as a critical domain for chemical-mediated activation of TRPV3. We also propose that carvacrol can function as a molecular tool in the design of novel specific TRPV3 modulators for the further understanding of TRPV3 channel pharmacology.  相似文献   
128.
Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.2×, NyuWa) and 2677 samples from the 1000 Genomes Project (∼7.4×, 1KGP). We discovered that LINE-1 insertions were highly enriched in centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.  相似文献   
129.
130.
Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5’untranslated region (5′UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufen1-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity.  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