全文获取类型
收费全文 | 747篇 |
免费 | 5篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 22篇 |
丛书文集 | 1篇 |
教育与普及 | 3篇 |
理论与方法论 | 8篇 |
现状及发展 | 79篇 |
研究方法 | 132篇 |
综合类 | 435篇 |
自然研究 | 75篇 |
出版年
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 9篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 12篇 |
2012年 | 55篇 |
2011年 | 130篇 |
2010年 | 11篇 |
2009年 | 9篇 |
2008年 | 55篇 |
2007年 | 63篇 |
2006年 | 57篇 |
2005年 | 70篇 |
2004年 | 67篇 |
2003年 | 54篇 |
2002年 | 68篇 |
2001年 | 1篇 |
1999年 | 8篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 5篇 |
1984年 | 1篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1970年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有755条查询结果,搜索用时 484 毫秒
61.
Thibault ST Singer MA Miyazaki WY Milash B Dompe NA Singh CM Buchholz R Demsky M Fawcett R Francis-Lang HL Ryner L Cheung LM Chong A Erickson C Fisher WW Greer K Hartouni SR Howie E Jakkula L Joo D Killpack K Laufer A Mazzotta J Smith RD Stevens LM Stuber C Tan LR Ventura R Woo A Zakrajsek I Zhao L Chen F Swimmer C Kopczynski C Duyk G Winberg ML Margolis J 《Nature genetics》2004,36(3):283-287
With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences. 相似文献
62.
The massive star that underwent a collapse of its core to produce supernova (SN)1993J was subsequently identified as a non-variable red supergiant star in images of the galaxy M81 taken before explosion. It showed an excess in ultraviolet and B-band colours, suggesting either the presence of a hot, massive companion star or that it was embedded in an unresolved young stellar association. The spectra of SN1993J underwent a remarkable transformation from the signature of a hydrogen-rich type II supernova to one of a helium-rich (hydrogen-deficient) type Ib. The spectral and photometric peculiarities were best explained by models in which the 13-20 solar mass supergiant had lost almost its entire hydrogen envelope to a close binary companion, producing a 'type IIb' supernova, but the hypothetical massive companion stars for this class of supernovae have so far eluded discovery. Here we report photometric and spectroscopic observations of SN1993J ten years after the explosion. At the position of the fading supernova we detect the unambiguous signature of a massive star: the binary companion to the progenitor. 相似文献
63.
Agricultural sustainability and intensive production practices 总被引:121,自引:0,他引:121
A doubling in global food demand projected for the next 50 years poses huge challenges for the sustainability both of food production and of terrestrial and aquatic ecosystems and the services they provide to society. Agriculturalists are the principal managers of global usable lands and will shape, perhaps irreversibly, the surface of the Earth in the coming decades. New incentives and policies for ensuring the sustainability of agriculture and ecosystem services will be crucial if we are to meet the demands of improving yields without compromising environmental integrity or public health. 相似文献
64.
Growth of early continental crust controlled by melting of amphibolite in subduction zones 总被引:68,自引:0,他引:68
It is thought that the first continental crust formed by melting of either eclogite or amphibolite, either at subduction zones or on the underside of thick oceanic crust. However, the observed compositions of early crustal rocks and experimental studies have been unable to distinguish between these possibilities. Here we show a clear contrast in trace-element ratios of melts derived from amphibolites and those from eclogites. Partial melting of low-magnesium amphibolite can explain the low niobium/tantalum and high zirconium/samarium ratios in melts, as required for the early continental crust, whereas the melting of eclogite cannot. This indicates that the earliest continental crust formed by melting of amphibolites in subduction-zone environments and not by the melting of eclogite or magnesium-rich amphibolites in the lower part of thick oceanic crust. Moreover, the low niobium/tantalum ratio seen in subduction-zone igneous rocks of all ages is evidence that the melting of rutile-eclogite has never been a volumetrically important process. 相似文献
65.
Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer 总被引:26,自引:0,他引:26
Tomlinson IP Alam NA Rowan AJ Barclay E Jaeger EE Kelsell D Leigh I Gorman P Lamlum H Rahman S Roylance RR Olpin S Bevan S Barker K Hearle N Houlston RS Kiuru M Lehtonen R Karhu A Vilkki S Laiho P Eklund C Vierimaa O Aittomäki K Hietala M Sistonen P Paetau A Salovaara R Herva R Launonen V Aaltonen LA;Multiple Leiomyoma Consortium 《Nature genetics》2002,30(4):406-410
66.
Vetter DE Li C Zhao L Contarino A Liberman MC Smith GW Marchuk Y Koob GF Heinemann SF Vale W Lee KF 《Nature genetics》2002,31(4):363-369
Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing. 相似文献
67.
Genome shuffling leads to rapid phenotypic improvement in bacteria 总被引:51,自引:0,他引:51
For millennia, selective breeding, on the basis of biparental mating, has led to the successful improvement of plants and animals to meet societal needs. At a molecular level, DNA shuffling mimics, yet accelerates, evolutionary processes, and allows the breeding and improvement of individual genes and subgenomic DNA fragments. We describe here whole-genome shuffling; a process that combines the advantage of multi-parental crossing allowed by DNA shuffling with the recombination of entire genomes normally associated with conventional breeding. We show that recursive genomic recombination within a population of bacteria can efficiently generate combinatorial libraries of new strains. When applied to a population of phenotypically selected bacteria, many of these new strains show marked improvements in the selected phenotype. We demonstrate the use of this approach through the rapid improvement of tylosin production from Streptomyces fradiae. This approach has the potential to facilitate cell and metabolic engineering and provide a non-recombinant alternative to the rapid production of improved organisms. 相似文献
68.
Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor coactivators 总被引:11,自引:0,他引:11
Demarest SJ Martinez-Yamout M Chung J Chen H Xu W Dyson HJ Evans RM Wright PE 《Nature》2002,415(6871):549-553
69.
Lamarre D Anderson PC Bailey M Beaulieu P Bolger G Bonneau P Bös M Cameron DR Cartier M Cordingley MG Faucher AM Goudreau N Kawai SH Kukolj G Lagacé L LaPlante SR Narjes H Poupart MA Rancourt J Sentjens RE St George R Simoneau B Steinmann G Thibeault D Tsantrizos YS Weldon SM Yong CL Llinàs-Brunet M 《Nature》2003,426(6963):186-189
Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics. 相似文献
70.
Programmed destruction of regulatory proteins through the ubiquitin-proteasome system is a widely used mechanism for controlling signalling pathways. Cullins are proteins that function as scaffolds for modular ubiquitin ligases typified by the SCF (Skp1-Cul1-F-box) complex. The substrate selectivity of these E3 ligases is dictated by a specificity module that binds cullins. In the SCF complex, this module is composed of Skp1, which binds directly to Cul1, and a member of the F-box family of proteins. F-box proteins bind Skp1 through the F-box motif, and substrates by means of carboxy-terminal protein interaction domains. Similarly, Cul2 and Cul5 interact with BC-box-containing specificity factors through the Skp1-like protein elongin C. Cul3 is required for embryonic development in mammals and Caenorhabditis elegans but its specificity module is unknown. Here we report the identification of a large family of BTB-domain proteins as substrate-specific adaptors for C. elegans CUL-3. Biochemical studies using the BTB protein MEL-26 and its genetic target MEI-1 (refs 12, 13) indicate that BTB proteins merge the functional properties of Skp1 and F-box proteins into a single polypeptide. 相似文献