全文获取类型
收费全文 | 2076篇 |
免费 | 165篇 |
国内免费 | 293篇 |
专业分类
2534篇 |
出版年
2024年 | 12篇 |
2023年 | 46篇 |
2022年 | 87篇 |
2021年 | 125篇 |
2020年 | 83篇 |
2019年 | 112篇 |
2018年 | 110篇 |
2017年 | 74篇 |
2016年 | 86篇 |
2015年 | 141篇 |
2014年 | 134篇 |
2013年 | 167篇 |
2012年 | 187篇 |
2011年 | 174篇 |
2010年 | 118篇 |
2009年 | 111篇 |
2008年 | 106篇 |
2007年 | 67篇 |
2006年 | 95篇 |
2005年 | 67篇 |
2004年 | 51篇 |
2003年 | 53篇 |
2002年 | 56篇 |
2001年 | 29篇 |
2000年 | 28篇 |
1999年 | 33篇 |
1998年 | 20篇 |
1997年 | 22篇 |
1996年 | 14篇 |
1995年 | 14篇 |
1994年 | 5篇 |
1993年 | 12篇 |
1992年 | 16篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1977年 | 2篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1969年 | 2篇 |
1964年 | 2篇 |
1960年 | 1篇 |
排序方式: 共有2534条查询结果,搜索用时 15 毫秒
41.
Laetitia Mathon Virginie Marques Stéphanie Manel Camille Albouy Marco Andrello Emilie Boulanger Julie Deter Régis Hocdé Fabien Leprieur Tom B. Letessier Nicolas Loiseau Eva Maire Alice Valentini Laurent Vigliola Florian Baletaud Sandra Bessudo Tony Dejean Nadia Faure Pierre-Edouard Guerin Meret Jucker Jean-Baptiste Juhel Kadarusman Andrea Polanco F. Laurent Pouyaud Dario Schwörer Kirsten F. Thompson Marc Troussellier Hagi Yulia Sugeha Laure Velez Xiaowei Zhang Wenjun Zhong Loïc Pellissier David Mouillot 《Global Ecology and Biogeography》2023,32(8):1336-1352
Aim
Coastal fishes have a fundamental role in marine ecosystem functioning and contributions to people, but face increasing threats due to climate change, habitat degradation and overexploitation. The extent to which human pressures are impacting coastal fish biodiversity in comparison with geographic and environmental factors at large spatial scale is still under scrutiny. Here, we took advantage of environmental DNA (eDNA) metabarcoding to investigate the relationship between fish biodiversity, including taxonomic and genetic components, and environmental but also socio-economic factors.Location
Tropical, temperate and polar coastal areas.Time period
Present day.Major taxa studied
Marine fishes.Methods
We analysed fish eDNA in 263 stations (samples) in 68 sites distributed across polar, temperate and tropical regions. We modelled the effect of environmental, geographic and socio-economic factors on α- and β-diversity. We then computed the partial effect of each factor on several fish biodiversity components using taxonomic molecular units (MOTU) and genetic sequences. We also investigated the relationship between fish genetic α- and β-diversity measured from our barcodes, and phylogenetic but also functional diversity.Results
We show that fish eDNA MOTU and sequence α- and β-diversity have the strongest correlation with environmental factors on coastal ecosystems worldwide. However, our models also reveal a negative correlation between biodiversity and human dependence on marine ecosystems. In areas with high dependence, diversity of all fish, cryptobenthic fish and large fish MOTUs declined steeply. Finally, we show that a sequence diversity index, accounting for genetic distance between pairs of MOTUs, within and between communities, is a reliable proxy of phylogenetic and functional diversity.Main conclusions
Together, our results demonstrate that short eDNA sequences can be used to assess climate and direct human impacts on marine biodiversity at large scale in the Anthropocene and can further be extended to investigate biodiversity in its phylogenetic and functional dimensions. 相似文献42.
本研究旨在探究非洲猪瘟病毒(African swine fever virus, ASFV) I226R蛋白(I226R protein, pI226R)抑制cGAS-STING信号通路的作用机制。利用双荧光素酶报告系统和实时荧光定量PCR (real-time quantitative PCR, qPCR)证明pI226R显著抑制cGAS-STING通路介导的I型干扰素及干扰素刺激相关基因的产生。免疫共沉淀及激光共聚焦显微镜试验发现pI226R与cGAS蛋白相互作用。免疫印迹分析证明pI226R通过自噬-溶酶体途径促进cGAS蛋白的降解。同时,pI226R阻碍了cGAS与E3泛素连接酶三基序蛋白56 (tripartite motif protein 56, TRIM56)的结合,导致cGAS的单泛素化减弱,从而抑制了cGAS的活化和cGAS-STING通路的激活。总之,本研究证明ASFV pI226R通过拮抗cGAS进而抑制宿主的抗病毒天然免疫反应,进一步增加了对研究ASFV免疫逃逸机制的理解,为疫苗的研发提供了理论基础。 相似文献
43.
Zhang Y Zhang Q Gao Y He X Kong H Jiang Y Guan Y Xia X Shu Y Kawaoka Y Bu Z Chen H 《Journal of virology》2012,86(18):9666-9674
Animal influenza viruses pose a clear threat to public health. Transmissibility among humans is a prerequisite for a novel influenza virus to cause a human pandemic. A novel reassortant swine influenza virus acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. However, the molecular aspects of influenza virus transmission remain poorly understood. Here, we show that an amino acid in hemagglutinin (HA) is important for the 2009 H1N1 influenza pandemic virus (2009/H1N1) to bind to human virus receptors and confer respiratory droplet transmissibility in mammals. We found that the change from glutamine (Q) to arginine (R) at position 226 of HA, which causes a switch in receptor-binding preference from human α-2,6 to avian α-2,3 sialic acid, resulted in a virus incapable of respiratory droplet transmission in guinea pigs and reduced the virus's ability to replicate in the lungs of ferrets. The change from alanine (A) to threonine (T) at position 271 of PB2 also abolished the virus's respiratory droplet transmission in guinea pigs, and this mutation, together with the HA Q226R mutation, abolished the virus's respiratory droplet transmission in ferrets. Furthermore, we found that amino acid 271A of PB2 plays a key role in virus acquisition of the mutation at position 226 of HA that confers human receptor recognition. Our results highlight the importance of both the PB2 and HA genes on the adaptation and transmission of influenza viruses in humans and provide important insights for monitoring and evaluating the pandemic potential of field influenza viruses. 相似文献
44.
Four new hetisine‐type C20‐diterpenoid alkaloids, named as coreanines A–D ( 1 – 4 ), were isolated from the roots of Aconitum coreanum, together with thirteen known alkaloids ( 5 – 17 ). Their structures were elucidated by extensive spectroscopic methods including IR, HR‐ESI‐MS and NMR techniques. All the isolated compounds were screened for the acetylcholinesterase (AChE) inhibitory effects, and none of them showed considerable inhibitory activity. 相似文献
45.
46.
Tetracyclines are aromatic polyketides biosynthesized by bacterial type II polyketide synthases. The amidated tetracycline backbone is biosynthesized by the minimal polyketide synthases and an amidotransferase homologue OxyD. Biosynthesis of the key intermediate 6-methylpretetramid requires two early tailoring steps, which are cyclization of the linearly fused tetracyclic scaffold and regioselective C-methylation of the aglycon. Using a heterologous host (CH999)/vector pair, we identified the minimum set of enzymes from the oxytetracycline biosynthetic pathway that is required to afford 6-methylpretetramid in vivo. Only two cyclases (OxyK and OxyN) are necessary to completely cyclize and aromatize the amidated tetracyclic aglycon. Formation of the last ring via C-1/C-18 aldol condensation does not require a dedicated fourth-ring cyclase, in contrast to the biosynthetic mechanism of other tetracyclic aromatic polyketides, such as daunorubicin and tetracenomycin. Acetyl-derived polyketides do not undergo spontaneous fourth-ring cyclization and form only anthracene carboxylic acids as demonstrated both in vivo and in vitro. OxyF was identified to be the C-6 C-methyltransferase that regioselectively methylates pretetramid to yield 6-methylpretetramid. Reconstitution of 6-methylpretetramid in a heterologous host sets the stage for a more systematic investigation of additional tetracycline downstream tailoring enzymes and is a key step toward the engineered biosynthesis of tetracycline analogs. 相似文献
47.
目的探讨宫颈病变患者阴道微生态与高危型HPV感染及宫颈癌相关增殖基因表达的相关性。方法选择2018年1月至2019年1月间在我院确诊为原发性宫颈癌的患者50例作为宫颈癌组,在我院诊断为宫颈糜烂的患者78例作为宫颈糜烂组,同期在我院进行体检的健康女性100例作为正常对照组。对比3组研究对象的阴道微生态失调率、高危型HPV感染率以及宫颈癌组、宫颈糜烂组患者宫颈病灶组织中宫颈癌相关增殖基因(Prdx4、Nek2、Fhit、BLCAP)mRNA表达量的差异。采用Pearson检验分析宫颈癌患者阴道微生态失调率与高危型HPV感染及宫颈癌相关增殖基因表达的相关性。结果宫颈癌组、宫颈糜烂组患者的阴道微生态失调率、高危型HPV感染率高于正常对照组,其中宫颈癌组患者这两项指标水平高于宫颈糜烂组(均P0.05)。宫颈癌组患者宫颈病灶组织中Prdx4、Nek2 mRNA表达量高于宫颈糜烂组,Fhit、BLCAP mRNA表达量低于宫颈糜烂组(均P0.05)。相关性分析发现,宫颈癌患者阴道微生态失调率与高危型HPV感染率呈正相关,与癌基因(Prdx4、Nek2)mRNA表达量呈正相关,与抑癌基因(Fhit、BLCAP)mRNA表达量呈负相关(均P0.05)。结论宫颈癌患者阴道微生态失调率较高,可能与高危型HPV感染及癌细胞增殖旺盛密切相关。 相似文献
48.
RNA聚合酶Ⅱ最大亚基Rpb1的羧基端结构域(carboxyl-terminal repeat domain,CTD)是RNA聚合酶Ⅱ发挥转录延伸功能所必需的,对其执行精确的转录调节功能至关重要。酵母细胞周期蛋白依赖性激酶CTDK-I(carboxyl-terminal repeat domain kinase,CTDK-I)由CTK1、CTK2和CTK3组成,作用于RNA聚合酶Ⅱ羧基端结构域,动态磷酸化CTD的七肽重复序列(YSPTSPS)来调控转录和翻译。酵母中的特异性蛋白CTK3与特殊的细胞周期蛋白CTK2结合形成异二聚体,再与CTDK-I的催化亚基CTK1结合以调节其活性。CTK1作为细胞周期蛋白CDK(cyclin dependent kinase,CDK)的同源蛋白,其结构与功能的研究可拓展人们对CDK蛋白家族的认识;CTK2-CTK3复合物对CTK1调控机制的研究也可为细胞周期蛋白抑制剂的研发提供新的思路。本文简述了酵母CTDK-I的功能特点及其亚基的结构与功能以及亚基间的相互作用,并展望了CTDK-I复合物的研究前景。 相似文献
49.
用PCR方法从油桐尺蠖核型多角体病毒 (BusuNPV)中扩增出DNA聚合酶基因片段 ,经pGEM T载体克隆到大肠杆菌DH5α菌株中。经自动序列分析仪测出DNA聚合酶基因 2 379bp长的核苷酸序列 ,推导出 793的氨基酸序列。氨基酸同源性比较显示 ,BusuNPV与HzSNPV的同源性最高 ,达 57% ;与OpMNPV的同源性最低 ,为 39.6 %。 相似文献
50.
Woo JA Jung AR Lakshmana MK Bedrossian A Lim Y Bu JH Park SA Koo EH Mook-Jung I Kang DE 《Cell death and differentiation》2012,19(9):1413-1423
Neurodegeneration associated with amyloid β (Aβ) peptide accumulation, synaptic loss, neuroinflammation, tauopathy, and memory impairments encompass the pathophysiological features of Alzheimer's disease (AD). We previously reported that the scaffolding protein RanBP9, which is overall increased in brains of AD patients, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating the endocytosis of amyloid precursor protein (APP) and β1-integrin, respectively. Here, we show that RanBP9 protein levels are increased by fourfold in FAD mutant APP transgenic mice. Accordingly, RanBP9 transgenic mice demonstrate significantly increased synapse loss, neurodegeneration, gliosis, and spatial memory deficits. RanBP9 overexpression promotes apoptosis and potentiates Aβ-induced neurotoxicity independent of its capacity to promote Aβ generation. Conversely, RanBP9 reduction by siRNA or gene dosage mitigates Aβ-induced neurotoxicity. Importantly, RanBP9 activates/dephosphorylates cofilin, a key regulator of actin dynamics and mitochondria-mediated apoptosis, and siRNA knockdown of cofilin abolishes both Aβ and RanBP9-induced apoptosis. These findings implicate the RanBP9-cofilin pathway as critical therapeutic targets not only for stemming Aβ generation but also antagonizing Aβ-induced neurotoxicity. 相似文献