全文获取类型
收费全文 | 1632篇 |
免费 | 20篇 |
国内免费 | 24篇 |
专业分类
系统科学 | 25篇 |
丛书文集 | 16篇 |
教育与普及 | 86篇 |
理论与方法论 | 9篇 |
现状及发展 | 162篇 |
研究方法 | 302篇 |
综合类 | 1075篇 |
自然研究 | 1篇 |
出版年
2022年 | 5篇 |
2021年 | 3篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 10篇 |
2016年 | 5篇 |
2015年 | 3篇 |
2013年 | 5篇 |
2012年 | 134篇 |
2011年 | 155篇 |
2010年 | 40篇 |
2009年 | 5篇 |
2008年 | 123篇 |
2007年 | 149篇 |
2006年 | 148篇 |
2005年 | 135篇 |
2004年 | 120篇 |
2003年 | 82篇 |
2002年 | 89篇 |
2001年 | 65篇 |
2000年 | 76篇 |
1999年 | 27篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 16篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1971年 | 3篇 |
1970年 | 7篇 |
1966年 | 6篇 |
1959年 | 15篇 |
1958年 | 29篇 |
1957年 | 18篇 |
1956年 | 20篇 |
1955年 | 17篇 |
1954年 | 23篇 |
1948年 | 10篇 |
1934年 | 2篇 |
排序方式: 共有1676条查询结果,搜索用时 421 毫秒
41.
Metabolic priming by a secreted fungal effector 总被引:1,自引:0,他引:1
Djamei A Schipper K Rabe F Ghosh A Vincon V Kahnt J Osorio S Tohge T Fernie AR Feussner I Feussner K Meinicke P Stierhof YD Schwarz H Macek B Mann M Kahmann R 《Nature》2011,478(7369):395-398
Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. maydis actively suppresses plant defence responses by secreted protein effectors. Its effector repertoire comprises at least 386 genes mostly encoding proteins of unknown function and expressed exclusively during the biotrophic stage. The U. maydis secretome also contains about 150 proteins with probable roles in fungal nutrition, fungal cell wall modification and host penetration as well as proteins unlikely to act in the fungal-host interface like a chorismate mutase. Chorismate mutases are key enzymes of the shikimate pathway and catalyse the conversion of chorismate to prephenate, the precursor for tyrosine and phenylalanine synthesis. Root-knot nematodes inject a secreted chorismate mutase into plant cells likely to affect development. Here we show that the chorismate mutase Cmu1 secreted by U. maydis is a virulence factor. The enzyme is taken up by plant cells, can spread to neighbouring cells and changes the metabolic status of these cells through metabolic priming. Secreted chorismate mutases are found in many plant-associated microbes and might serve as general tools for host manipulation. 相似文献
42.
Consequences of climate change on the tree of life in Europe 总被引:2,自引:0,他引:2
Many species are projected to become vulnerable to twenty-first-century climate changes, with consequent effects on the tree of life. If losses were not randomly distributed across the tree of life, climate change could lead to a disproportionate loss of evolutionary history. Here we estimate the consequences of climate change on the phylogenetic diversities of plant, bird and mammal assemblages across Europe. Using a consensus across ensembles of forecasts for 2020, 2050 and 2080 and high-resolution phylogenetic trees, we show that species vulnerability to climate change clusters weakly across phylogenies. Such phylogenetic signal in species vulnerabilities does not lead to higher loss of evolutionary history than expected with a model of random extinctions. This is because vulnerable species have neither fewer nor closer relatives than the remaining clades. Reductions in phylogenetic diversity will be greater in southern Europe, and gains are expected in regions of high latitude or altitude. However, losses will not be offset by gains and the tree of life faces a trend towards homogenization across the continent. 相似文献
43.
44.
Programming the magnitude and persistence of antibody responses with innate immunity 总被引:1,自引:0,他引:1
Kasturi SP Skountzou I Albrecht RA Koutsonanos D Hua T Nakaya HI Ravindran R Stewart S Alam M Kwissa M Villinger F Murthy N Steel J Jacob J Hogan RJ García-Sastre A Compans R Pulendran B 《Nature》2011,470(7335):543-547
Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques. 相似文献
45.
46.
47.
48.
Horvath A Boikos S Giatzakis C Robinson-White A Groussin L Griffin KJ Stein E Levine E Delimpasi G Hsiao HP Keil M Heyerdahl S Matyakhina L Libè R Fratticci A Kirschner LS Cramer K Gaillard RC Bertagna X Carney JA Bertherat J Bossis I Stratakis CA 《Nature genetics》2006,38(7):794-800
Phosphodiesterases (PDEs) regulate cyclic nucleotide levels. Increased cyclic AMP (cAMP) signaling has been associated with PRKAR1A or GNAS mutations and leads to adrenocortical tumors and Cushing syndrome. We investigated the genetic source of Cushing syndrome in individuals with adrenocortical hyperplasia that was not caused by known defects. We performed genome-wide SNP genotyping, including the adrenocortical tumor DNA. The region with the highest probability to harbor a susceptibility gene by loss of heterozygosity (LOH) and other analyses was 2q31-2q35. We identified mutations disrupting the expression of the PDE11A isoform-4 gene (PDE11A) in three kindreds. Tumor tissues showed 2q31-2q35 LOH, decreased protein expression and high cyclic nucleotide levels and cAMP-responsive element binding protein (CREB) phosphorylation. PDE11A codes for a dual-specificity PDE that is expressed in adrenal cortex and is partially inhibited by tadalafil and other PDE inhibitors; its germline inactivation is associated with adrenocortical hyperplasia, suggesting another means by which dysregulation of cAMP signaling causes endocrine tumors. 相似文献
49.
Regulation of primary cilia formation and left-right patterning in zebrafish by a noncanonical Wnt signaling mediator, duboraya 总被引:1,自引:0,他引:1
Oishi I Kawakami Y Raya A Callol-Massot C Izpisúa Belmonte JC 《Nature genetics》2006,38(11):1316-1322
Primary cilia are microtubule-based organelles that project from the surface of nearly every animal cell. Although important functions of primary cilia in morphogenesis and tissue homeostasis have been identified, the mechanisms that control the formation of primary cilia are not understood. Here we characterize a zebrafish gene, termed duboraya (dub), that is essential for ciliogenesis. Knockdown of dub in zebrafish embryos results in both defects in primary cilia formation in Kupffer's vesicle and randomization of left-right organ asymmetries. We show that, at the molecular level, the function of dub in ciliogenesis is regulated by phosphorylation, which in turn depends on Frizzled-2-mediated noncanonical Wnt signaling. We also provide evidence that, at the cellular level, dub function is essential for actin organization in the cells lining Kupffer's vesicle. Taken together, our findings identify a molecular factor that links noncanonical Wnt signaling with the control of left-right axis specification, and provide an entry point for analyzing the mechanisms that regulate primary cilia formation. 相似文献
50.
Sayer JA Otto EA O'Toole JF Nurnberg G Kennedy MA Becker C Hennies HC Helou J Attanasio M Fausett BV Utsch B Khanna H Liu Y Drummond I Kawakami I Kusakabe T Tsuda M Ma L Lee H Larson RG Allen SJ Wilkinson CJ Nigg EA Shou C Lillo C Williams DS Hoppe B Kemper MJ Neuhaus T Parisi MA Glass IA Petry M Kispert A Gloy J Ganner A Walz G Zhu X Goldman D Nurnberg P Swaroop A Leroux MR Hildebrandt F 《Nature genetics》2006,38(6):674-681