全文获取类型
收费全文 | 411篇 |
免费 | 43篇 |
出版年
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 10篇 |
2018年 | 17篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 19篇 |
2014年 | 18篇 |
2013年 | 21篇 |
2012年 | 16篇 |
2011年 | 22篇 |
2010年 | 14篇 |
2009年 | 17篇 |
2008年 | 17篇 |
2007年 | 15篇 |
2006年 | 16篇 |
2005年 | 13篇 |
2004年 | 10篇 |
2003年 | 18篇 |
2002年 | 13篇 |
2001年 | 6篇 |
2000年 | 10篇 |
1999年 | 6篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1992年 | 13篇 |
1991年 | 4篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 6篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 9篇 |
1980年 | 3篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1954年 | 2篇 |
排序方式: 共有454条查询结果,搜索用时 687 毫秒
41.
42.
Fournier A Florin A Lefebvre C Solly F Leroux D Callanan MB 《Cytogenetic and genome research》2007,118(2-4):320-327
Recently, we and others have described a novel class of chromosome aberrations that involves constitutive heterochromatin on human chromosome 1 (cytogenetic band 1q12). These anomalies are particularly frequent in B cell non-Hodgkins lymphoma (NHL) and multiple myeloma (MM) and, remarkably, almost invariably involve partial or total gain of chromosome 1q (including 1q12 heterochromatin) and the formation of novel heterochromatin/euchromatin junctions. This review discusses the pathological significance of these anomalies in light of i) recent integrated gene expression and array comparative genomic hybridisation (aCGH) profiling in MM and ii) increasing evidence of a key role for heterochromatin in the control of normal and pathological gene silencing. 相似文献
43.
44.
Ciliopathies are pleiotropic and genetically heterogeneous disorders caused by defective development and function of the primary cilium. Bardet-Biedl syndrome (BBS) proteins localize to the base of cilia and undergo intraflagellar transport, and the loss of their functions leads to a multisystemic ciliopathy. Here we report the identification of mutations in guanylate cyclases (GCYs) as modifiers of Caenorhabditis elegans bbs endophenotypes. The loss of GCY-35 or GCY-36 results in suppression of the small body size, developmental delay, and exploration defects exhibited by multiple bbs mutants. Moreover, an effector of cGMP signalling, a cGMP-dependent protein kinase, EGL-4, also modifies bbs mutant defects. We propose that a misregulation of cGMP signalling, which underlies developmental and some behavioural defects of C. elegans bbs mutants, may also contribute to some BBS features in other organisms. 相似文献
45.
Le Bihan-Duval E Nadaf J Berri C Pitel F Graulet B Godet E Leroux SY Demeure O Lagarrigue S Duby C Cogburn LA Beaumont CM Duclos MJ 《PloS one》2011,6(7):e14825
Classical quantitative trait loci (QTL) analysis and gene expression QTL (eQTL) were combined to identify the causal gene (or QTG) underlying a highly significant QTL controlling the variation of breast meat color in a F2 cross between divergent high-growth (HG) and low-growth (LG) chicken lines. Within this meat quality QTL, BCMO1 (Accession number GenBank: AJ271386), encoding the β-carotene 15, 15'-monooxygenase, a key enzyme in the conversion of β-carotene into colorless retinal, was a good functional candidate. Analysis of the abundance of BCMO1 mRNA in breast muscle of the HG x LG F2 population allowed for the identification of a strong cis eQTL. Moreover, reevaluation of the color QTL taking BCMO1 mRNA levels as a covariate indicated that BCMO1 mRNA levels entirely explained the variations in meat color. Two fully-linked single nucleotide polymorphisms (SNP) located within the proximal promoter of BCMO1 gene were identified. Haplotype substitution resulted in a marked difference in BCMO1 promoter activity in vitro. The association study in the F2 population revealed a three-fold difference in BCMO1 expression leading to a difference of 1 standard deviation in yellow color between the homozygous birds at this haplotype. This difference in meat yellow color was fully consistent with the difference in carotenoid content (i.e. lutein and zeaxanthin) evidenced between the two alternative haplotypes. A significant association between the haplotype, the level of BCMO1 expression and the yellow color of the meat was also recovered in an unrelated commercial broiler population. The mutation could be of economic importance for poultry production by making possible a gene-assisted selection for color, a determining aspect of meat quality. Moreover, this natural genetic diversity constitutes a new model for the study of β-carotene metabolism which may act upon diverse biological processes as precursor of the vitamin A. 相似文献
46.
Elisabeth Le Bihan-Duval Javad Nadaf Cécile Berri Frédérique Pitel Beno?t Graulet Estelle Godet Sophie Y. Leroux Olivier Demeure Sandrine Lagarrigue Cécile Duby Larry A. Cogburn Catherine M. Beaumont Michel J. Duclos 《PloS one》2011,6(7)
Classical quantitative trait loci (QTL) analysis and gene expression QTL (eQTL) were combined to identify the causal gene (or QTG) underlying a highly significant QTL controlling the variation of breast meat color in a F2 cross between divergent high-growth (HG) and low-growth (LG) chicken lines. Within this meat quality QTL, BCMO1 (Accession number GenBank: ), encoding the β-carotene 15, 15′-monooxygenase, a key enzyme in the conversion of β-carotene into colorless retinal, was a good functional candidate. Analysis of the abundance of BCMO1 mRNA in breast muscle of the HG x LG F2 population allowed for the identification of a strong cis eQTL. Moreover, reevaluation of the color QTL taking BCMO1 mRNA levels as a covariate indicated that BCMO1 mRNA levels entirely explained the variations in meat color. Two fully-linked single nucleotide polymorphisms (SNP) located within the proximal promoter of BCMO1 gene were identified. Haplotype substitution resulted in a marked difference in BCMO1 promoter activity in vitro. The association study in the F2 population revealed a three-fold difference in BCMO1 expression leading to a difference of 1 standard deviation in yellow color between the homozygous birds at this haplotype. This difference in meat yellow color was fully consistent with the difference in carotenoid content (i.e. lutein and zeaxanthin) evidenced between the two alternative haplotypes. A significant association between the haplotype, the level of BCMO1 expression and the yellow color of the meat was also recovered in an unrelated commercial broiler population. The mutation could be of economic importance for poultry production by making possible a gene-assisted selection for color, a determining aspect of meat quality. Moreover, this natural genetic diversity constitutes a new model for the study of β-carotene metabolism which may act upon diverse biological processes as precursor of the vitamin A. AJ271386相似文献
47.
48.
Beaumont C Roussot O Feve K Vignoles F Leroux S Pitel F Faure JM Mills AD Guémené D Sellier N Mignon-Grasteau S Le Roy P Vignal A 《Animal genetics》2005,36(5):401-407
A quantitative trait loci (QTL) study was undertaken to identify genome regions involved in the control of fearfulness in Japanese quail (Coturnix japonica). An F2 cross was made between two quail lines divergently selected over 29 generations on duration of tonic immobility (DTI), a catatonic-like state of reduced responsiveness to a stressful stimulation. A total of 1065 animals were measured for the logarithm of DTI (LOGTI), the number of inductions (NI) necessary to induce the immobility reaction, open-field behaviour including locomotor activity (MOVE), latency before first movement (LAT), number of jumps (JUMP), dejections (DEJ) and shouts (SHOUT), corticosterone level after a contention stress (LOGCORT) and body weight at 2 weeks of age (BW2). A total of 310 animals were included in a genome scan using selective genotyping with 248 AFLP markers. A total of 21 suggestive or genome-wide significant QTL were observed. Two highly significant QTL were identified on linkage group 1 (GL1), one for LOGTI and one for NI. In the vicinity of the QTL for LOGTI, a nearly significant QTL for SHOUT and a suggestive QTL for LAT were also identified. On GL3, genome-wide significant QTL were observed for JUMP and DEJ as well as suggestive QTL for LOGTI, MOVE, SHOUT and LAT. A significant QTL for BW2 was observed on GL2 and a nearly significant one on GL1. These results may be useful in the understanding of fearfulness in quail and related species provided that fearfulness has the same genetic basis. 相似文献
49.
Stirling PC Bakhoum SF Feigl AB Leroux MR 《Nature structural & molecular biology》2006,13(10):865-870
Molecular chaperones have evolved diverse tertiary and quaternary structures to stabilize non-native polypeptides and facilitate their transition to the native state. Indeed, different families of chaperones lack sequence similarity, and few are represented ubiquitously in all three domains of life. Despite their discrete evolutionary paths, recent crystal structures reveal that many chaperones use seemingly convergent strategies to bind non-native proteins. This crystallographic evidence shows, or strongly suggests, that chaperones including prefoldin, Skp, trigger factor, Hsp40 and Hsp90 have clamp-like structural features used to grip substrate proteins. We explore the notion that clamp-like structures are evolutionarily favored by both ATP-dependent and ATP-independent molecular chaperones. Presumably, clamps present a multivalent binding surface ideal for protecting unstable protein conformers until they reach the native state or are transferred to another component of the folding machinery. 相似文献
50.
Viaud M Fillinger S Liu W Polepalli JS Le Pêcheur P Kunduru AR Leroux P Legendre L 《Molecular plant-microbe interactions : MPMI》2006,19(9):1042-1050
Filamentous ascomycetes contain large numbers of histidine kinases (HK) that belong to eleven classes. Members of class III from different species were previously shown to be involved in osmoregulation and resistance to dicarboximide and phenylpyrrole fungicides. We have inactivated the gene encoding the single group III HK, BOS1, in the economically important plant pathogen Botrytis cinerea. BOS1 inactivation had pleiotropic effects on the fungus. Besides the expected osmosensitivity and resistance to fungicides, null mutants presented additional characteristics indicating that BOS1 is necessary for normal macroconidiation and full virulence. On standard culture media, null mutants very rarely formed conidiophores and those few conidiophores failed to produce conidia. This defect could be partially restored with 1 M sorbitol, suggesting that another BOS1-independent signal cascade may be involved in macroconidiation. The mutants were not found to be hypersensitive to various oxidative stresses but were more resistant to menadione. Finally, pathogenicity tests showed that bos1-null mutants were significantly reduced in the ability to infect host plants. Appressorium morphogenesis was not altered; however, in planta growth was severely reduced. To our knowledge, this is the first class III HK characterized as a pathogenicity factor in a plant-pathogenic ascomycete. 相似文献