全文获取类型
收费全文 | 291篇 |
免费 | 28篇 |
出版年
2022年 | 2篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 14篇 |
2013年 | 7篇 |
2012年 | 21篇 |
2011年 | 17篇 |
2010年 | 11篇 |
2009年 | 12篇 |
2008年 | 16篇 |
2007年 | 18篇 |
2006年 | 24篇 |
2005年 | 13篇 |
2004年 | 16篇 |
2003年 | 16篇 |
2002年 | 12篇 |
1999年 | 2篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1980年 | 6篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 3篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1962年 | 1篇 |
1960年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有319条查询结果,搜索用时 15 毫秒
21.
The mechanism of the angiotensin-converting enzyme inhibitor quinapril is not related to bradykinin level in heart tissue 总被引:2,自引:0,他引:2
Barthelemy C Eurin J Lechat P Masson F Cortines M Mougenot N Soualmia H Carayon A 《Peptides》2002,23(6):1161-1169
In order to examine the effect of the angiotensin-converting enzyme inhibitor (ACEi) quinapril, we performed a sensitive and specific radioimmunoassay (RIA) to quantify bradykinin, BK-(1-9), in heart and kidney tissues. The BK-(1-9) level was unaffected in the heart of sham and water-deprived rats treated for 2h with quinapril (10mg/kg), but was significantly higher in the kidneys in the two groups. In these conditions, circulating and tissue angiotensin II (Ang II) levels were significantly decreased by quinapril. Moreover, our results indicated that acute treatment with this dose of quinapril induced kinin-mediated effects which were not related to its action on bradykinin degradation in rat hearts. 相似文献
22.
Saveanu C Namane A Gleizes PE Lebreton A Rousselle JC Noaillac-Depeyre J Gas N Jacquier A Fromont-Racine M 《Molecular and cellular biology》2003,23(13):4449-4460
Ribosome biogenesis in eukaryotes depends on the coordinated action of ribosomal and nonribosomal proteins that guide the assembly of preribosomal particles. These intermediate particles follow a maturation pathway in which important changes in their protein composition occur. The mechanisms involved in the coordinated assembly of the ribosomal particles are poorly understood. We show here that the association of preribosomal factors with pre-60S complexes depends on the presence of earlier factors, a phenomenon essential for ribosome biogenesis. The analysis of the composition of purified preribosomal complexes blocked in maturation at specific steps allowed us to propose a model of sequential protein association with, and dissociation from, early pre-60S complexes for several preribosomal factors such as Mak11, Ssf1, Rlp24, Nog1, and Nog2. The presence of either Ssf1 or Nog2 in complexes that contain the 27SB pre-rRNA defines novel, distinct pre-60S particles that contain the same pre-rRNA intermediates and that differ only by the presence or absence of specific proteins. Physical and functional interactions between Rlp24 and Nog1 revealed that the assembly steps are, at least in part, mediated by direct protein-protein interactions. 相似文献
23.
Mark C. Ball Laura Finnegan Micheline Manseau Paul Wilson 《Conservation Genetics》2010,11(6):2131-2143
Individual-based clustering (IBC) methods have become increasingly popular for the characterization and delineation of genetic
population units for numerous species. These methods delineate populations based on the genetic assumptions of a breeding
unit which may provide a better representation of the behaviour of the species. The increasing use of IBC has resulted in
the development of several analytical models all of which vary in their theoretical assumptions to infer genetic population
structure. In this paper, we report a comparative strategy utilizing three IBC methods to characterize the spatial genetic
structure of the boreal population of woodland caribou (Rangifer tarandus caribou) in central Canada. In addition, we implement both tests for isolation-by-distance (IBD) and frequency-based assignment tests
to validate the consensus genetic clusters as defined by IBC. We also compare indirect metrics of genetic diversity and gene
flow using both a priori defined herds and the IBC defined populations. Although our results show some concordance between both pre-defined herds
and IBC derived genetic clusters, the IBC analyses identified a cluster that was cryptic to observation-based caribou herds
and found no difference between several adjacent herds. By comparing multiple IBC methods and integrating both IBD and indirect
genetic diversity metrics a posteriori, our strategy provides an effective means to delineate wildlife population structure and accurately assess genetic diversity
and connectivity. 相似文献
24.
Raja Brauner Anu Bashamboo Sébastien Rouget Marie Goulet Pascal Philibert Hélène Sarda-Thibault Christine Trivin Micheline Misrahi Charles Sultan Ken McElreavey 《PloS one》2010,5(6)
Background
The cause of isolated gonadotropin-independent precocious puberty (PP) with an ovarian cyst is unknown in the majority of cases. Here, we describe 11 new cases of peripheral PP and, based on phenotypes observed in mouse models, we tested the hypothesis that mutations in the GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX may be associated with this phenotype.Methodology/Principal Findings
11 girls with gonadotropin-independent PP were included in this study. Three girls were seen for a history of prenatal ovarian cyst, 6 girls for breast development, and 2 girls for vaginal bleeding. With one exception, all girls were seen before 8 years of age. In 8 cases, an ovarian cyst was detected, and in one case, suspected. One other case has polycystic ovaries, and the remaining case was referred for vaginal bleeding. Four patients had a familial history of ovarian anomalies and/or infertility. Mutations in the coding sequences of the candidate genes GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX were not observed.Conclusions/Significance
Ovarian PP shows markedly different clinical features from central PP. Our data suggest that mutations in the GNAS1, NR5A1, LHCGR, FSHR StAR, DMRT4 and NOBOX genes are not responsible for ovarian PP. Further research, including the identification of familial cases, is needed to understand the etiology of ovarian PP. 相似文献25.
The p21-activated protein kinase inhibitor Skb15 and its budding yeast homologue are 60S ribosome assembly factors 下载免费PDF全文
Saveanu C Rousselle JC Lenormand P Namane A Jacquier A Fromont-Racine M 《Molecular and cellular biology》2007,27(8):2897-2909
Ribosome biogenesis is driven by a large number of preribosomal factors that associate with and dissociate from the preribosomal particles along the maturation pathway. We have previously shown that budding yeast Mak11, whose homologues in other eukaryotes were described as modulating a p21-activated protein kinase function, accumulates in Rlp24-associated pre-60S complexes when their maturation is impeded in Saccharomyces cerevisiae. The functional inactivation of WD40 repeat protein Mak11 interfered with the 60S rRNA maturation, led to a cell cycle delay in G(1), and blocked green fluorescent protein-tagged Rpl25 in the nucleoli of yeast cells, indicating an early role of Mak11 in ribosome assembly. Surprisingly, Mak11 inactivation also led to a dramatic destabilization of Rlp24. The suppression of the thermosensitive phenotype of a mak11 mutant by RLP24 overexpression and a direct in vitro interaction between Rlp24 and Mak11 suggest that Mak11 acts as an Rlp24 cofactor during early steps of 60S ribosomal subunit assembly. Moreover, we found that Skb15, the Mak11 homologue in Schizosaccharomyces pombe, also associated with preribosomes and affected 60S biogenesis in fission yeast. It is thus likely that the previously observed phenotypes for MAK11 homologues in other eukaryotes are secondary to the main function of these proteins in ribosome formation. 相似文献
26.
Ribosome biogenesis is a major conserved cellular pathway that requires both ribosomal proteins and many preribosomal factors. Most of the pre-60S factors are recycled into the nucleus; some of them shuttle between the nucleus and the cytoplasm while a few others, like Rei1, are strictly cytoplasmic and are mostly involved in the dissociation/recycling of the pre-60S shuttling factors. Here, we investigated the role of the Jjj1 Hsp40 chaperone in ribosome biogenesis. The absence of Jjj1 leads to a cold sensitive phenotype, a defect in the relative amount of the large ribosomal subunit with the appearance of halfmers, and to cytoplasmic accumulation of shuttling factors such as Arx1 and Alb1, which stay bound to the pre-60S particles. Jjj1 is, thus, a novel pre-60S factor involved in the last cytoplasmic steps of the large ribosomal subunit biogenesis. We report the biochemical association of Jjj1 and Rei1 to similar pre-60S complexes, their two-hybrid interactions, and their functional links. Altogether, these results indicate that Rei1 and Jjj1 share many common features. However, while the functions of Jjj1 and Rei1 partially overlap, we could distinguish specific role of the two proteins in Arx1/Alb1 and Tif6 recycling. We propose that Jjj1 is preferentially required for the release of Arx1 and Alb1 shuttling factors from the cytoplasmic pre-60S particles while Rei1 is preferentially involved in their recycling. 相似文献
27.
28.
Fonseca Bárbara Medeiros Câmara Paulo Eduardo Aguiar Saraiva Ogaki Mayara Baptistucci Pinto Otávio Henrique Bezerra Lirio Juan Manuel Coria Silvia H. Vieira Rosemary Carvalho-Silva Micheline Amorim Eduardo Toledo Convey Peter Rosa Luiz Henrique 《Molecular biology reports》2022,49(1):179-188
Molecular Biology Reports - Vega Island is located off the eastern tip of the Antarctic Peninsula (Maritime Antarctica), in the Weddell Sea. In this study, we used metabarcoding to investigate... 相似文献
29.
Wésolowski-Louvel M 《FEMS yeast research》2011,11(6):509-513
Kluyveromyces lactis strains impaired in the nonhomologous end-joining pathway are relevant tools for the homologous integration of exogenous DNA into the genome, as in the mutant strains, close to 100% of the integrants are targeted to the homologous locus, compared with a few per cent for the wild-type recipient. Using a loxP-kanMX-loxP cassette together with a Cre-recombinase plasmid, a nej1∷loxP mutant strain suitable for multiple gene disruption has been constructed. Furthermore, using this strain, PCR-generated constructs with only 50 bp of homologous flanking sequences resulted in efficient exogenous DNA targeting. 相似文献
30.