全文获取类型
收费全文 | 161篇 |
免费 | 43篇 |
专业分类
204篇 |
出版年
2022年 | 4篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 9篇 |
2013年 | 7篇 |
2012年 | 7篇 |
2011年 | 7篇 |
2010年 | 12篇 |
2009年 | 11篇 |
2008年 | 9篇 |
2007年 | 9篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 9篇 |
2003年 | 9篇 |
2002年 | 2篇 |
2001年 | 3篇 |
2000年 | 10篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1960年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有204条查询结果,搜索用时 15 毫秒
1.
Summary There is much more variation in the composition of bird communities in the earlier open and semi-open seral stages of ecological successions in forested landscapes of Europe than later on in preforested and forested climactic stages. The demonstration of this trend is achieved from the study of four habitat gradients, two in the mediterranean region (Provence and Corsica) and two in central Europe (Burgundy, France and Poland). A multivariate analysis has been used to illustrate the dynamics of communities along these succession. Displays of the results in bivariate space as well as an illustration of the distributional profiles of some of the most characteristic species show that: i) there is a discrimination between the two mediterranean gradients and the two medioeuropean ones and ii) each succession starts with a very distinct set of species and then the four gradients regularly converge in the last climactic stage where there is almost no discrimination between communities. These results are discussed in the light of the history of European biotas during the Pleistocene. The reason why there is more variation in species composition in the earlier seral stages than in the later forested stages are discussed according to current theories on the role of habitat selection on speciation processes. 相似文献
2.
Molecular characterization of mouse-virulent poliovirus type 1 Mahoney mutants: involvement of residues of polypeptides VP1 and VP2 located on the inner surface of the capsid protein shell. 总被引:13,自引:12,他引:1 下载免费PDF全文
Most poliovirus (PV) strains, including PV PV-1/Mahoney, are unable to cause paralysis in mice. Determinants for restriction of PV-1/Mahoney in mice have been identified by manipulating PV-1 cDNA and located on the viral capsid protein VP1. These determinants consist of a highly exposed amino acid sequence on the capsid surface corresponding to the B-C loop (M. Murray, J. Bradley, X. Yang, E. Wimmer, E. Moss, and V. Racaniello, Science 241:213-215, 1988; A. Martin, C. Wychowski, T. Couderc, R. Crainic, J. Hogle, and M. Girard, EMBO J. 7:2839-2847, 1988) and of residues belonging to the N-terminal sequence located on the inner surface of the protein shell (E. Moss and V. Racaniello, EMBO J. 10:1067-1074, 1991). Using an in vivo approach, we isolated two mouse-neurovirulent PV-1 mutants in the mouse central nervous system after a single passage of PV-1/Mahoney inoculated by the intracerebral route. Both mutants were subjected to two additional passages in mice, plaque purified, and subsequently characterized. The two cloned mutants, Mah-NK13 and Mah-NL32, retained phenotypic characteristics of the parental PV-1/Mahoney, including epitope map, heat lability, and temperature sensitivity. Mah-NK13 exhibited slightly smaller plaques than did the parental virus. The nucleotide sequences of the mutant genomes were determined, and mutations were identified. Mutations were independently introduced into the parental PV-1/Mahoney genome by single-site mutagenesis. Mutated PV-1/Mahoney viruses were then tested for their neurovirulence in mice. A single amino acid substitution in the capsid proteins VP1 (Thr-22-->Ile) and VP2 (Ser-31-->Thr) identified in the Mah-NK13 and Mah-NL32 genomes, respectively, conferred the mouse-virulent phenotype to the mouse-avirulent PV-1/Mahoney. Ile-22 in VP1 was responsible for the small-plaque phenotype of Mah-NK13. Both mutations arose during the first passage in the mouse central nervous system. We thus identified a new mouse adaptation determinant on capsid protein VP1, and we showed that at least one other capsid protein, VP2, could also express a mouse adaptation determinant. Both determinants are located in the inside of the three-dimensional structure of the viral capsid. They may be involved in the early steps of mouse nerve cell infection subsequent to receptor attachment. 相似文献
3.
Mouse mammary tumor gene int-3: a member of the notch gene family transforms mammary epithelial cells. 总被引:13,自引:0,他引:13 下载免费PDF全文
Expression of a 2.3-kb RNA species is induced in mammary tumors as a consequence of insertional mutagenesis at the int-3 locus by the mouse mammary tumor virus. The nucleotide sequence and biological activity of this mammary tumor-specific int-3 RNA species were determined. It contains an open reading frame which encodes a 57-kDa protein. The translated protein possesses six nearly contiguous 32-amino-acid repeats which are related to a similar motif in the Saccharomyces cerevisiae cdc-10-encoded cell cycle protein. In addition, the int-3 cdc-10 repeats are bounded by the PEST amino acid sequence motif which is commonly found in proteins having a rapid turnover and may represent sites for phosphorylation. The int-3 cdc-10 repeat sequences are 50% identical to a portion of the intracellular domain of the neurogenic Drosophila notch gene product. Activation of expression of a recombinant int-3 genomic DNA fragment encoding the 2.3-kb RNA species in HC11 mouse mammary epithelial cells in vitro induces anchorage-independent growth in soft agar. 相似文献
4.
By comparison with deciduous oaks, the lower yearly production of new leaves in sclerophyllous oaks is hypothesized to have several consequences on animal communities. In particular, the production of arthropod communities that feed upon the leaves should be lower in sclerophyllous than in deciduous oaks, this causing changes in breeding patterns and the demographic balance in insectivorous birds. Studies in both deciduous and sclerophyllous habitats in southern France have shown that: 1) the spring development of new leaves occurs later and more slowly in sclerophyllous than in deciduous oaks, 2) the biomass of caterpillars is much lower in sclerophyllous oak forests, and 3) there is a large variation in life history traits of the Blue Tit depending in which type of habitat they breed. Laying date occurs later and clutch size is lower in sclerophyllous habitats than in deciduous habitats. The evolution of life history traits is discussed according to whether poor sclerophyllous habitats are isolated (e.g. on Corsica) or are parts of landscapes including both habitat types. 相似文献
5.
E J Niesor C B Wollheim D H Mintz B Blondel A E Renold R Weil 《The Biochemical journal》1979,178(3):559-568
The feasibility of infection and transformation by SV40 (simian virus 40) of primary cell cultures derived from newborn-rat pancreas was investigated. As judged by the presence of intranuclear SV40 T-antigen, exposure to the virus resulted specifically in infection and transformation of epithelioid (predominantly endocrine) cells. The transformed cells were subcultured (more than 64 passages) and cloned. Culture medium and acid/ethanol extracts of the cells did not contain detectable amounts of immunoreactive insulin after the third subculture. However, inoculation of such SV40-transformed pancreatic cells into immunodeficient rats results in tumours in which insulin production was partially restored through the passage in vivo, since the tumour cells contained and synthesized small amounts of immunoreactive insulin which co-migrated with an insulin marker on gel chromatography. Interestingly, the transformed cells maintained under tissue-culture conditions produced a protein immunologically related to insulin, soluble in aqueous buffer but insoluble in acid/ethanol. This 3000-dalton protein is too large to be a translation product of the rat preproinsulin 9S mRNA. SV40-transformed pancreatic cells might prove useful in the investigation of the factors controlling and maintaining insulin biosynthesis. 相似文献
6.
The mouse int-2 gene exhibits basic fibroblast growth factor activity in a basic fibroblast growth factor-responsive cell line 总被引:2,自引:0,他引:2
7.
Nissan X Blondel S Navarro C Maury Y Denis C Girard M Martinat C De Sandre-Giovannoli A Levy N Peschanski M 《Cell reports》2012,2(1):1-9
One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS), who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage. 相似文献
8.
9.
Fran?ois Téoulé Cynthia Brisac Isabelle Pelletier Pierre-Olivier Vidalain Sophie Jégouic Carmen Mirabelli Ma?l Bessaud Nicolas Combelas Arnaud Autret Frédéric Tangy Francis Delpeyroux Bruno Blondel 《Journal of virology》2013,87(20):11031-11046
We have shown that the circulating vaccine-derived polioviruses responsible for poliomyelitis outbreaks in Madagascar have recombinant genomes composed of sequences encoding capsid proteins derived from poliovaccine Sabin, mostly type 2 (PVS2), and sequences encoding nonstructural proteins derived from other human enteroviruses. Interestingly, almost all of these recombinant genomes encode a nonstructural 3A protein related to that of field coxsackievirus A17 (CV-A17) strains. Here, we investigated the repercussions of this exchange, by assessing the role of the 3A proteins of PVS2 and CV-A17 and their putative cellular partners in viral replication. We found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), recently identified as an interactor for the 3A proteins of several picornaviruses, interacts with the 3A proteins of PVS2 and CV-A17 at viral RNA replication sites, in human neuroblastoma cells infected with either PVS2 or a PVS2 recombinant encoding a 3A protein from CV-A17 [PVS2-3A(CV-A17)]. The small interfering RNA-mediated downregulation of ACBD3 significantly increased the growth of both viruses, suggesting that ACBD3 slowed viral replication. This was confirmed with replicons. Furthermore, PVS2-3A(CV-A17) was more resistant to the replication-inhibiting effect of ACBD3 than the PVS2 strain, and the amino acid in position 12 of 3A was involved in modulating the sensitivity of viral replication to ACBD3. Overall, our results indicate that exchanges of nonstructural proteins can modify the relationships between enterovirus recombinants and cellular interactors and may thus be one of the factors favoring their emergence. 相似文献
10.
Armand Berneman Lory Montout Sophie Goyard Nathalie Chamond Alain Cosson Simon d’Archivio Nicolas Gouault Philippe Uriac Arnaud Blondel Paola Minoprio 《PloS one》2013,8(4)
Chagas’ disease is caused by Trypanosoma cruzi, a protozoan transmitted to humans by blood-feeding insects, blood transfusion or congenitally. Previous research led us to discover a parasite proline racemase (TcPRAC) and to establish its validity as a target for the design of new chemotherapies against the disease, including its chronic form. A known inhibitor of proline racemases, 2-pyrrolecarboxylic acid (PYC), is water-insoluble. We synthesized soluble pyrazole derivatives, but they proved weak or inactive TcPRAC inhibitors. TcPRAC catalytic site is too small and constrained when bound to PYC to allow efficient search for new inhibitors by virtual screening. Forty-nine intermediate conformations between the opened enzyme structure and the closed liganded one were built by calculating a transition path with a method we developed. A wider range of chemical compounds could dock in the partially opened intermediate active site models in silico. Four models were selected for known substrates and weak inhibitors could dock in them and were used to screen chemical libraries. Two identified soluble compounds, (E)-4-oxopent-2-enoic acid (OxoPA) and its derivative (E)-5-bromo-4-oxopent-2-enoic acid (Br-OxoPA), are irreversible competitive inhibitors that presented stronger activity than PYC on TcPRAC. We show here that increasing doses of OxoPA and Br-OxoPA hamper T. cruzi intracellular differentiation and fate in mammalian host cells. Our data confirm that through to their binding mode, these molecules are interesting and promising as lead compounds for the development of chemotherapies against diseases where active proline racemases play essential roles. 相似文献