全文获取类型
收费全文 | 397篇 |
免费 | 0篇 |
专业分类
系统科学 | 11篇 |
丛书文集 | 1篇 |
理论与方法论 | 13篇 |
现状及发展 | 35篇 |
研究方法 | 120篇 |
综合类 | 207篇 |
自然研究 | 10篇 |
出版年
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 2篇 |
2013年 | 4篇 |
2012年 | 54篇 |
2011年 | 59篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 51篇 |
2007年 | 27篇 |
2006年 | 24篇 |
2005年 | 29篇 |
2004年 | 37篇 |
2003年 | 20篇 |
2002年 | 20篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有397条查询结果,搜索用时 78 毫秒
191.
192.
193.
194.
The codon 72 polymorphic variants of p53 have markedly different apoptotic potential 总被引:31,自引:0,他引:31
The gene TP53, encoding p53, has a common sequence polymorphism that results in either proline or arginine at amino-acid position 72. This polymorphism occurs in the proline-rich domain of p53, which is necessary for the protein to fully induce apoptosis. We found that in cell lines containing inducible versions of alleles encoding the Pro72 and Arg72 variants, and in cells with endogenous p53, the Arg72 variant induces apoptosis markedly better than does the Pro72 variant. Our data indicate that at least one source of this enhanced apoptotic potential is the greater ability of the Arg72 variant to localize to the mitochondria; this localization is accompanied by release of cytochrome c into the cytosol. These data indicate that the two polymorphic variants of p53 are functionally distinct, and these differences may influence cancer risk or treatment. 相似文献
195.
Ludwig A Debus L Lieckfeldt D Wirgin I Benecke N Jenneckens I Williot P Waldman JR Pitra C 《Nature》2002,419(6906):447-448
The two species of Atlantic sea sturgeon on either shore of the North Atlantic, Acipenser sturio in Europe and A. oxyrinchus in North America, probably diverged with the closure of the Tethys Sea and the onset of the North Atlantic Gyre 15-20 million years ago, and contact between them was then presumably precluded by geographic distance. Here we present genetic, morphological and archaeological evidence indicating that the North American sturgeon colonized the Baltic during the Middle Ages and replaced the native sturgeon there, before recently becoming extinct itself in Europe as a result of human activities. In addition to representing a unique transatlantic colonization event by a fish that swims upriver to spawn, our findings have important implications for projects aimed at restocking Baltic waters with the European sturgeon. 相似文献
196.
Genetic and structural analyses suggest that a novel SPG3A mutation causes severe phenotypes of hereditary spastic paraplegia 总被引:2,自引:0,他引:2
CHEN Suqin ZHOU Yan LI Xunhua Labu HUANG Shuang HUANG Weijun ZHOU Chunlong MAXWELL Patrick H WANG Yiming 《科学通报(英文版)》2006,51(16):2038-2040
Hereditary spastic paraplegia (HSP) (MIM# 182600, etc.) is a group of heterogeneous neurodegenerative disorders, characterized by lower limb spasticity, hy- perreflexia, progressive spastic gait abnormalities and an extensor-plantar response[1]. The genot… 相似文献
197.
McClelland M Sanderson KE Clifton SW Latreille P Porwollik S Sabo A Meyer R Bieri T Ozersky P McLellan M Harkins CR Wang C Nguyen C Berghoff A Elliott G Kohlberg S Strong C Du F Carter J Kremizki C Layman D Leonard S Sun H Fulton L Nash W Miner T Minx P Delehaunty K Fronick C Magrini V Nhan M Warren W Florea L Spieth J Wilson RK 《Nature genetics》2004,36(12):1268-1274
Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae). 相似文献
198.
Adams DJ Biggs PJ Cox T Davies R van der Weyden L Jonkers J Smith J Plumb B Taylor R Nishijima I Yu Y Rogers J Bradley A 《Nature genetics》2004,36(8):867-871
Embryonic stem cell technology revolutionized biology by providing a means to assess mammalian gene function in vivo. Although it is now routine to generate mice from embryonic stem cells, one of the principal methods used to create mutations, gene targeting, is a cumbersome process. Here we describe the indexing of 93,960 ready-made insertional targeting vectors from two libraries. 5,925 of these vectors can be used directly to inactivate genes with an average targeting efficiency of 28%. Combinations of vectors from the two libraries can be used to disrupt both alleles of a gene or engineer larger genomic changes such as deletions, duplications, translocations or inversions. These indexed vectors constitute a public resource (Mutagenic Insertion and Chromosome Engineering Resource; MICER) for high-throughput, targeted manipulation of the mouse genome. 相似文献
199.
Postcopulatory sperm competition is a key aspect of sexual selection and is believed to drive the rapid evolution of both reproductive physiology and reproduction-related genes. It is well-established that mating behavior determines the intensity of sperm competition, with polyandry (i.e., female promiscuity) leading to fiercer sperm competition than monandry. Studies in mammals, particularly primates, showed that, owing to greater sperm competition, polyandrous taxa generally have physiological traits that make them better adapted for fertilization than monandrous species, including bigger testes, larger seminal vesicles, higher sperm counts, richer mitochondrial loading in sperm and more prominent semen coagulation. Here, we show that the degree of polyandry can also impact the dynamics of molecular evolution. Specifically, we show that the evolution of SEMG2, the gene encoding semenogelin II, a main structural component of semen coagulum, is accelerated in polyandrous primates relative to monandrous primates. Our study showcases the intimate relationship between sexual selection and the molecular evolution of reproductive genes. 相似文献
200.
Seo HC Edvardsen RB Maeland AD Bjordal M Jensen MF Hansen A Flaat M Weissenbach J Lehrach H Wincker P Reinhardt R Chourrout D 《Nature》2004,431(7004):67-71
Tunicate embryos and larvae have small cell numbers and simple anatomical features in comparison with other chordates, including vertebrates. Although they branch near the base of chordate phylogenetic trees, their degree of divergence from the common chordate ancestor remains difficult to evaluate. Here we show that the tunicate Oikopleura dioica has a complement of nine Hox genes in which all central genes are lacking but a full vertebrate-like set of posterior genes is present. In contrast to all bilaterians studied so far, Hox genes are not clustered in the Oikopleura genome. Their expression occurs mostly in the tail, with some tissue preference, and a strong partition of expression domains in the nerve cord, in the notochord and in the muscle. In each tissue of the tail, the anteroposterior order of Hox gene expression evokes spatial collinearity, with several alterations. We propose a relationship between the Hox cluster breakdown, the separation of Hox expression domains, and a transition to a determinative mode of development. 相似文献