全文获取类型
收费全文 | 17588篇 |
免费 | 2083篇 |
国内免费 | 4篇 |
出版年
2021年 | 239篇 |
2019年 | 144篇 |
2018年 | 182篇 |
2017年 | 189篇 |
2016年 | 303篇 |
2015年 | 462篇 |
2014年 | 545篇 |
2013年 | 705篇 |
2012年 | 838篇 |
2011年 | 887篇 |
2010年 | 558篇 |
2009年 | 488篇 |
2008年 | 715篇 |
2007年 | 755篇 |
2006年 | 696篇 |
2005年 | 658篇 |
2004年 | 627篇 |
2003年 | 619篇 |
2002年 | 573篇 |
2001年 | 489篇 |
2000年 | 512篇 |
1999年 | 445篇 |
1998年 | 267篇 |
1997年 | 223篇 |
1996年 | 198篇 |
1995年 | 189篇 |
1994年 | 182篇 |
1993年 | 204篇 |
1992年 | 386篇 |
1991年 | 296篇 |
1990年 | 339篇 |
1989年 | 297篇 |
1988年 | 316篇 |
1987年 | 326篇 |
1986年 | 261篇 |
1985年 | 287篇 |
1984年 | 232篇 |
1983年 | 256篇 |
1982年 | 222篇 |
1981年 | 191篇 |
1980年 | 179篇 |
1979年 | 246篇 |
1978年 | 216篇 |
1977年 | 186篇 |
1976年 | 184篇 |
1975年 | 176篇 |
1974年 | 172篇 |
1973年 | 187篇 |
1972年 | 163篇 |
1971年 | 137篇 |
排序方式: 共有10000条查询结果,搜索用时 187 毫秒
991.
Allison Jones Andrew E. Teschendorff Quanxi Li Jane D. Hayward Athilakshmi Kannan Tim Mould James West Michal Zikan David Cibula Heidi Fiegl Shih-Han Lee Elisabeth Wik Richard Hadwin Rupali Arora Charlotte Lemech Henna Turunen P?ivi Pakarinen Ian J. Jacobs Helga B. Salvesen Milan K. Bagchi Indrani C. Bagchi Martin Widschwendter 《PLoS medicine》2013,10(11)
992.
Brandon Faubert Gino Boily Said Izreig Takla Griss Bozena Samborska Zhifeng Dong Fanny Dupuy Christopher Chambers Benjamin J. Fuerth Benoit Viollet Orval A. Mamer Daina Avizonis Ralph J. DeBerardinis Peter M. Siegel Russell G. Jones 《Cell metabolism》2013,17(1):113-124
Highlights? Loss of AMPKα1 cooperates with the Myc oncogene to accelerate lymphomagenesis ? AMPKα dysfunction enhances aerobic glycolysis (Warburg effect) ? Inhibiting HIF-1α reverses the metabolic effects of AMPKα loss ? HIF-1α mediates the growth advantage of tumors with reduced AMPK signaling 相似文献
993.
Claudine Porta Abhay Kotecha Alison Burman Terry Jackson Jingshan Ren Silvia Loureiro Ian M. Jones Elizabeth E. Fry David I. Stuart Bryan Charleston 《PLoS pathogens》2013,9(3)
Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals. 相似文献
994.
Rosalie Moody Ying Zhu Yufei Huang Xiaodong Cui Tiffany Jones Roble Bedolla Xiufen Lei Zhiqiang Bai Shou-Jiang Gao 《PLoS pathogens》2013,9(12)
Kaposi''s sarcoma-associated herpesvirus (KSHV) is causally linked to several human cancers, including Kaposi''s sarcoma, primary effusion lymphoma and multicentric Castleman''s disease, malignancies commonly found in HIV-infected patients. While KSHV encodes diverse functional products, its mechanism of oncogenesis remains unknown. In this study, we determined the roles KSHV microRNAs (miRs) in cellular transformation and tumorigenesis using a recently developed KSHV-induced cellular transformation system of primary rat mesenchymal precursor cells. A mutant with a cluster of 10 precursor miRs (pre-miRs) deleted failed to transform primary cells, and instead, caused cell cycle arrest and apoptosis. Remarkably, the oncogenicity of the mutant virus was fully restored by genetic complementation with the miR cluster or several individual pre-miRs, which rescued cell cycle progression and inhibited apoptosis in part by redundantly targeting IκBα and the NF-κB pathway. Genomic analysis identified common targets of KSHV miRs in diverse pathways with several cancer-related pathways preferentially targeted. These works define for the first time an essential viral determinant for KSHV-induced oncogenesis and identify NF-κB as a critical pathway targeted by the viral miRs. Our results illustrate a common theme of shared functions with hierarchical order among the KSHV miRs. 相似文献
995.
996.
Chao Li Adam Schmidt Eran Pichersky Feng Shi A. Daniel Jones 《Metabolomics : Official journal of the Metabolomic Society》2013,9(1):92-101
Discrimination of isomeric methylated metabolites is an important step toward identifying genes responsible for methylation, but presents substantial challenges because authentic standards are often unavailable and mass spectra of isomers have been considered indistinguishable. In this report, an approach is described for identifying methyl group positions in multiply methylated flavonoid metabolites using combinations of tandem mass spectrometry, liquid chromatography retention, and site-selective methylation by recombinant O-methyltransferases from Solanum habrochaites LA1777. The basis for observed fragment ions in tandem mass spectra of multiply methylated myricetin was further established using enzymatic incorporation of deuterium-labeled methyl groups using S-adenosylmethionine-d 3 as precursor. 相似文献
997.
Multiple single case reports of asphyxiation in dolphins caused by fish lodged in the esophagus exist. However, the significance of this cause of mortality in a single population has not been documented. We performed a retrospective evaluation of pathology records from stranded bottlenose dolphins (Tursiops truncatus) from the Indian River Lagoon to evaluate the impact of this cause of death on this population. From 1997 to 2011, asphyxiation due to choking was identified as the cause of death in 14 of 350 cases (4%). Sampling of an unrelated but adjacent population over this same period yielded 186 necropsy cases of bottlenose dolphins with no cases of asphyxiation. Asphyxiated animals presented with a fish lodged in the cranial esophagus associated with a dislocated and obstructed or compressed larynx. There was no clear sex predilection. Affected animals included 12 adults and two juveniles. The fish species involved included sheepshead, black chin tilapia and striped mojarra. In five cases, recreational fishing gear was also present. Cetacean choking is related to selection of prey fish species with strong dorsal spines and may be secondarily associated with fish attached to fishing gear. Prey abundance and dolphin behavior may influence these selections. Environmental alterations leading to changes in prey availability or increased interactions with fishing gear may change the significance of fatal choking in dolphin populations. 相似文献
998.
Emmanuel S. Buys Yu-Chieh Ko Clemens Alt Sarah R. Hayton Alexander Jones Laurel T. Tainsh Ruiyi Ren Andrea Giani Maeva Clerté Emma Abernathy Robert E. T. Tainsh Dong-Jin Oh Rajeev Malhotra Pankaj Arora Nadine de Waard Binglan Yu Raphael Turcotte Daniel Nathan Marielle Scherrer-Crosbie Stephanie J. Loomis Jae H. Kang Charles P. Lin Haiyan Gong Douglas J. Rhee Peter Brouckaert Janey L. Wiggs Meredith S. Gregory Louis R. Pasquale Kenneth D. Bloch Bruce R. Ksander 《PloS one》2013,8(3)
Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG. 相似文献
999.
1000.
Idrish Ali Patrick O'Brien Gaurav Kumar Thomas Zheng Nigel C. Jones Didier Pinault Chris French Margaret J. Morris Michael R. Salzberg Terence J. O'Brien 《PloS one》2013,8(6)
Early life stress results in an enduring vulnerability to kindling-induced epileptogenesis in rats, but the underlying mechanisms are not well understood. Recent studies indicate the involvement of thalamocortical neuronal circuits in the progression of kindling epileptogenesis. Therefore, we sought to determine in vivo the effects of early life stress and amygdala kindling on the firing pattern of hippocampus as well as thalamic and cortical neurons. Eight week old male Wistar rats, previously exposed to maternal separation (MS) early life stress or early handling (EH), underwent amygdala kindling (or sham kindling). Once fully kindled, in vivo juxtacellular recordings in hippocampal, thalamic and cortical regions were performed under neuroleptic analgesia. In the thalamic reticular nucleus cells both kindling and MS independently lowered firing frequency and enhanced burst firing. Further, burst firing in the thalamic reticular nucleus was significantly increased in kindled MS rats compared to kindled EH rats (p<0.05). In addition, MS enhanced burst firing of hippocampal pyramidal neurons. Following a stimulation-induced seizure, somatosensory cortical neurons exhibited a more pronounced increase in burst firing in MS rats than in EH rats. These data demonstrate changes in firing patterns in thalamocortical and hippocampal regions resulting from both MS and amygdala kindling, which may reflect cellular changes underlying the enhanced vulnerability to kindling in rats that have been exposed to early life stress. 相似文献