全文获取类型
收费全文 | 120篇 |
免费 | 1篇 |
国内免费 | 2篇 |
学科分类
自然科学 | 123篇 |
出版年
2020年 | 1篇 |
2019年 | 1篇 |
2016年 | 1篇 |
2013年 | 2篇 |
2012年 | 7篇 |
2011年 | 10篇 |
2009年 | 2篇 |
2008年 | 6篇 |
2007年 | 4篇 |
2006年 | 9篇 |
2005年 | 4篇 |
2004年 | 2篇 |
2003年 | 8篇 |
2002年 | 2篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 6篇 |
1968年 | 1篇 |
1967年 | 6篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1961年 | 1篇 |
排序方式: 共有123条查询结果,搜索用时 15 毫秒
101.
Sebaihia M Wren BW Mullany P Fairweather NF Minton N Stabler R Thomson NR Roberts AP Cerdeño-Tárraga AM Wang H Holden MT Wright A Churcher C Quail MA Baker S Bason N Brooks K Chillingworth T Cronin A Davis P Dowd L Fraser A Feltwell T Hance Z Holroyd S Jagels K Moule S Mungall K Price C Rabbinowitsch E Sharp S Simmonds M Stevens K Unwin L Whithead S Dupuy B Dougan G Barrell B Parkhill J 《Nature genetics》2006,38(7):779-786
We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism. 相似文献
102.
Sharp AJ Hansen S Selzer RR Cheng Z Regan R Hurst JA Stewart H Price SM Blair E Hennekam RC Fitzpatrick CA Segraves R Richmond TA Guiver C Albertson DG Pinkel D Eis PS Schwartz S Knight SJ Eichler EE 《Nature genetics》2006,38(9):1038-1042
Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders. We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in four individuals. Using oligonucleotide arrays, we refined the breakpoints of this microdeletion, defining a 478-kb critical region containing six genes that were deleted in all four individuals. We mapped the breakpoints of this deletion and of four other pathogenic rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental duplications, suggesting that these are also sites of recurrent rearrangement. In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions. 相似文献
103.
Vivian JP Duncan RC Berry R O'Connor GM Reid HH Beddoe T Gras S Saunders PM Olshina MA Widjaja JM Harpur CM Lin J Maloveste SM Price DA Lafont BA McVicar DW Clements CS Brooks AG Rossjohn J 《Nature》2011,479(7373):401-405
Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have a pivotal role in innate immune responses. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0-D1-D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies. Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B*5701 complexed with a self-peptide. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B*5701 antigen-binding cleft, resulting in two discontinuous footprints on the pHLA. First, the D0 domain, a distinguishing feature of the KIR3D family, extended towards β2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an 'innate HLA sensor' domain. Second, whereas the D2-HLA-B*5701 interface exhibited a high degree of complementarity, the D1-pHLA-B*5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule. Although the two-domain KIR (KIR2D) and KIR3DL1 docked similarly onto HLA-C and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes. Collectively, in association with extensive mutagenesis studies at the KIR3DL1-pHLA-B*5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species. 相似文献
104.
Ten plant communities containing bitter nightshade ( Solanum dulcamara ) were studied and the ecology and naturalizing relationships of bitter nightshade in central Utah area were investigated. Biotic and abiotic factors from each area were statistically analyzed. The data indicated that bitter nightshade was negatively correlated (P 相似文献
105.
Kimberly A. Dodds Karen M. Clancy Kathryn J. Leyva David Greenberg Peter W. Price 《西北部美国博物学家》2011,56(2)
The western spruce budworm ( Choristoneura occidentalis Freeman) prefers to feed on flushing buds and current-year needles of Douglas-fir ( Pseudotsuga menziesii [Mirb.] Franco). Budworm larvae will not typically consume older age classes of needles unless all current-year foliage is depleted. We tested the following null hypotheses: (1) budworm larvae can feed on foliage with a wide range of qualities (i.e., current 1-, 2-, or 3-year-old needles) without measurable effects on fitness; and (2) budworm adults do not show any oviposition preference linked to the age of the foliage they fed on as larvae. We used both laboratory and field experiments. There was strong evidence to support rejection of hypothesis 1. Budworm larvae had greater survival from the 4th instar to pupal stage when they fed on current-year foliage (43%-52% survival) versus older age classes of foliage (0-25% survival). Pupae from current-year foliage were also heavier than pupae from ≥ 1-year-old foliage. There was weak evidence to support rejecting hypothesis 2; budworm adults that fed had fed on current-year or 3-year-old foliage as larvae preferred to oviposit on current-year foliage. Similar conclusions were drawn from the laboratory and field experiments. 相似文献
106.
Huw Price 《Studies in History and Philosophy of Science Part B: Studies in History and Philosophy of Modern Physics》2012,43(2):75-83
It has often been suggested that retrocausality offers a solution to some of the puzzles of quantum mechanics: e.g., that it allows a Lorentz-invariant explanation of Bell correlations, and other manifestations of quantum nonlocality, without action-at-a-distance. Some writers have argued that time-symmetry counts in favour of such a view, in the sense that retrocausality would be a natural consequence of a truly time-symmetric theory of the quantum world. Critics object that there is complete time-symmetry in classical physics, and yet no apparent retrocausality. Why should the quantum world be any different?This note throws some new light on these matters. I call attention to a respect in which quantum mechanics is different, under some assumptions about quantum ontology. Under these assumptions, the combination of time-symmetry without retrocausality is unavailable in quantum mechanics, for reasons intimately connected with the differences between classical and quantum physics (especially the role of discreteness in the latter). Not all interpretations of quantum mechanics share these assumptions, however, and in those that do not, time-symmetry does not entail retrocausality. 相似文献
107.
Garnett MJ Edelman EJ Heidorn SJ Greenman CD Dastur A Lau KW Greninger P Thompson IR Luo X Soares J Liu Q Iorio F Surdez D Chen L Milano RJ Bignell GR Tam AT Davies H Stevenson JA Barthorpe S Lutz SR Kogera F Lawrence K McLaren-Douglas A Mitropoulos X Mironenko T Thi H Richardson L Zhou W Jewitt F Zhang T O'Brien P Boisvert JL Price S Hur W Yang W Deng X Butler A Choi HG Chang JW Baselga J Stamenkovic I Engelman JA Sharma SV Delattre O Saez-Rodriguez J Gray NS Settleman J Futreal PA Haber DA 《Nature》2012,483(7391):570-575
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies. 相似文献
108.
Baur JA Pearson KJ Price NL Jamieson HA Lerin C Kalra A Prabhu VV Allard JS Lopez-Lluch G Lewis K Pistell PJ Poosala S Becker KG Boss O Gwinn D Wang M Ramaswamy S Fishbein KW Spencer RG Lakatta EG Le Couteur D Shaw RJ Navas P Puigserver P Ingram DK de Cabo R Sinclair DA 《Nature》2006,444(7117):337-342
Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing. 相似文献
109.
Summary Reducible compounds, probably similar to lysine-derived cross-links found in collagen and elastin, have been detected in an invertebrate scleroprotein, the egg case ofBuccinum undatum (L.)During this studyN. R. Price was in receipt of an S.R.C. research assistantship. 相似文献
110.