全文获取类型
收费全文 | 289篇 |
免费 | 38篇 |
国内免费 | 1篇 |
出版年
2021年 | 3篇 |
2020年 | 4篇 |
2018年 | 4篇 |
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 12篇 |
2014年 | 11篇 |
2013年 | 22篇 |
2012年 | 17篇 |
2011年 | 16篇 |
2010年 | 16篇 |
2009年 | 14篇 |
2008年 | 15篇 |
2007年 | 10篇 |
2006年 | 7篇 |
2005年 | 11篇 |
2004年 | 11篇 |
2003年 | 8篇 |
2002年 | 6篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 4篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1990年 | 4篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 6篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1968年 | 1篇 |
1966年 | 2篇 |
1910年 | 1篇 |
排序方式: 共有328条查询结果,搜索用时 114 毫秒
31.
Phares TW Kean RB Mikheeva T Hooper DC 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(12):7666-7675
The loss of blood-brain barrier (BBB) integrity in CNS inflammatory responses triggered by infection and autoimmunity has generally been associated with the development of neurological signs. In the present study, we demonstrate that the clearance of the attenuated rabies virus CVS-F3 from the CNS is an exception; increased BBB permeability and CNS inflammation occurs in the absence of neurological sequelae. We speculate that regionalization of the CNS inflammatory response contributes to its lack of pathogenicity. Despite virus replication and the expression of several chemokines and IL-6 in both regions being similar, the up-regulation of MIP-1beta, TNF-alpha, IFN-gamma, and ICAM-1 and the loss of BBB integrity was more extensive in the cerebellum than in the cerebral cortex. The accumulation of CD4- and CD19-positive cells was higher in the cerebellum than the cerebral cortex. Elevated CD19 levels were paralleled by kappa-L chain expression levels. The timing of BBB permeability changes, kappa-L chain expression in CNS tissues, and Ab production in the periphery suggest that the in situ production of virus-neutralizing Ab may be more important in virus clearance than the infiltration of circulating Ab. The data indicate that, with the possible exception of CD8 T cells, the effectors of rabies virus clearance are more commonly targeted to the cerebellum. This is likely the result of differences in the capacity of the tissues of the cerebellum and cerebral cortex to mediate the events required for BBB permeability changes and cell invasion during virus infection. 相似文献
32.
STK25 Protein Mediates TrkA and CCM2 Protein-dependent Death in Pediatric Tumor Cells of Neural Origin 总被引:1,自引:0,他引:1
B Costa MJ Kean V Ast JD Knight A Mett Z Levy DF Ceccarelli BG Badillo R Eils R König AC Gingras M Fainzilber 《The Journal of biological chemistry》2012,287(35):29285-29289
The TrkA receptor tyrosine kinase induces death in medulloblastoma cells via an interaction with the cerebral cavernous malformation 2 (CCM2) protein. We used affinity proteomics to identify the germinal center kinase class III (GCKIII) kinases STK24 and STK25 as novel CCM2 interactors. Down-modulation of STK25, but not STK24, rescued medulloblastoma cells from NGF-induced TrkA-dependent cell death, suggesting that STK25 is part of the death-signaling pathway initiated by TrkA and CCM2. CCM2 can be phosphorylated by STK25, and the kinase activity of STK25 is required for death signaling. Finally, STK25 expression in tumors is correlated with positive prognosis in neuroblastoma patients. These findings delineate a death-signaling pathway downstream of neurotrophic receptor tyrosine kinases that may provide targets for therapeutic intervention in pediatric tumors of neural origin. 相似文献
33.
Johnson ZP Eady RD Ahmad SF Agravat S Morris T Else J Lank SM Wiseman RW O'Connor DH Penedo MC Larsen CP Kean LS 《Immunogenetics》2012,64(4):329-336
Here we describe the Immunogenetic Management Software (IMS) system, a novel web-based application that permits multiplexed analysis of complex immunogenetic traits that are necessary for the accurate planning and execution of experiments involving large animal models, including nonhuman primates. IMS is capable of housing complex pedigree relationships, microsatellite-based MHC typing data, as well as MHC pyrosequencing expression analysis of class I alleles. It includes a novel, automated MHC haplotype naming algorithm and has accomplished an innovative visualization protocol that allows users to view multiple familial and MHC haplotype relationships through a single, interactive graphical interface. Detailed DNA and RNA-based data can also be queried and analyzed in a highly accessible fashion, and flexible search capabilities allow experimental choices to be made based on multiple, individualized and expandable immunogenetic factors. This web application is implemented in Java, MySQL, Tomcat, and Apache, with supported browsers including Internet Explorer and Firefox on Windows and Safari on Mac OS. The software is freely available for distribution to noncommercial users by contacting Leslie.kean@emory.edu. A demonstration site for the software is available at http://typing.emory.edu/typing_demo , user name: imsdemo7@gmail.com and password: imsdemo. 相似文献
34.
Different domains of the RNA polymerase of infectious bursal disease virus contribute to virulence 总被引:1,自引:0,他引:1
Nouën CL Toquin D Müller H Raue R Kean KM Langlois P Cherbonnel M Eterradossi N 《PloS one》2012,7(1):e28064
BACKGROUND: Infectious bursal disease virus (IBDV) is a pathogen of worldwide significance to the poultry industry. IBDV has a bi-segmented double-stranded RNA genome. Segments A and B encode the capsid, ribonucleoprotein and non-structural proteins, or the virus polymerase (RdRp), respectively. Since the late eighties, very virulent (vv) IBDV strains have emerged in Europe inducing up to 60% mortality. Although some progress has been made in understanding the molecular biology of IBDV, the molecular basis for the pathogenicity of vvIBDV is still not fully understood. METHODOLOGY, PRINCIPAL FINDINGS: Strain 88180 belongs to a lineage of pathogenic IBDV phylogenetically related to vvIBDV. By reverse genetics, we rescued a molecular clone (mc88180), as pathogenic as its parent strain. To study the molecular basis for 88180 pathogenicity, we constructed and characterized in vivo reassortant or mosaic recombinant viruses derived from the 88180 and the attenuated Cu-1 IBDV strains. The reassortant virus rescued from segments A of 88180 (A88) and B of Cu-1 (BCU1) was milder than mc88180 showing that segment B is involved in 88180 pathogenicity. Next, the exchange of different regions of BCU1 with their counterparts in B88 in association with A88 did not fully restore a virulence equivalent to mc88180. This demonstrated that several regions if not the whole B88 are essential for the in vivo pathogenicity of 88180. CONCLUSION, SIGNIFICANCE: The present results show that different domains of the RdRp, are essential for the in vivo pathogenicity of IBDV, independently of the replication efficiency of the mosaic viruses. 相似文献
35.
36.
Cost-effective surveillance strategies are needed for efficient responses to biological invasions and must account for the trade-offs between surveillance effort and management costs. Less surveillance may allow greater population growth and spread prior to detection, thereby increasing the costs of damages and control. In addition, surveillance strategies are usually applied in environments under continual invasion pressure where the number, size and location of established populations are unknown prior to detection. We develop a novel modeling framework that accounts for these features of the decision and invasion environment and determines the long term sampling effort that minimises the total expected costs of new invasions. The optimal solution depends on population establishment and growth rates, sample sensitivity, and sample, eradication, and damage costs. We demonstrate how to optimise surveillance systems under budgetary constraints and find that accounting for spatial heterogeneity in sampling costs and establishment rates can greatly reduce management costs. 相似文献
37.
Zhang ZF Matsuda D Khoo SK Buzzitta K Block E Petillo D Richard S Anema J Furge KA Teh BT 《Mutation research》2008,657(1):77-83
Cytogenetic abnormalities, such as DNA amplifications and deletions, often lead to significant changes in gene expression levels within a chromosomal region. Instead of generating additional DNA copy number data, one method to identify DNA copy number abnormalities has been to search existing gene expression data for regional perturbations in gene expression. However, it is not clear how well this surrogate method performs in the examination of individual tumors and how we can use both DNA and RNA data to identify candidate genes that may be mutated. Here we report a comparison study using summarized DNA and RNA data to identify chromosomal abnormalities in human samples. Forty-four tissue samples from patients diagnosed as having renal cell carcinoma (RCC) were collected, together with 15 normal kidney samples as controls, and for each sample the genome-wide DNA and RNA data were obtained for comparison using Affymetrix 100K SNP and HGU133plus2 gene expression chips, respectively. The DNA and RNA data was summarized by both chromosome arm and cytogenetic banding patterns and compared. The result of this analysis revealed that the two summarized data sets used to identify cytogenetic changes agreed well. However, some differences between the two were also identified. These differences of large-scale gene expression deregulation without evidence of the comparable DNA copy number alterations may be the result of known mechanisms, such as large-scale methylation or chromosome inactivation, or may be the result of some new mechanism of DNA-RNA translation. The usefulness of the combined data set for identifying regions of mutated genes is also discussed. 相似文献
38.
The 'invasiveness' of an alien species depends partly on its ability to become abundant and widespread in its new environment. While competitiveness may be an important component of this ability, so too is the abundance of resource or habitat. First, the local carrying capacity will depend on the local favourability of the habitat, hence the global density will depend on how widespread the habitat is. Second, and more subtly, the local density will also be affected by the global extent of favourable habitat, because of losses occasioned by dispersal when the population redistributes; these losses should be fewer the greater the contiguous area of favourable habitat or the more patches of such habitat across the landscape. Here we describe a model which demonstrates how habitat availability affects an invading speciesèquilibrium abundance, hence its invasiveness. The model shows that local density is likely to be an increasing function of global habitat abundance, and global density to be a non-linear, concave-up function of global habitat abundance. Examples are given to support the model's predictions, taken largely from alien species in New Zealand. 相似文献
39.
40.
Inhibition of yeast binding to mouse peritoneal macrophages by wheat germ agglutinin: a novel effect of the lectin on phagocytic cells 总被引:1,自引:0,他引:1
The ability of wheat germ agglutinin (WGA) to enhance the binding of bacteria and tumor cells to phagocytic cells, and to induce the killing of tumor cells by macrophages and monocytes, is well established. We observed, however, that WGA inhibits the binding to and phagocytosis of yeast cells by thioglycolate-elicited murine peritoneal macrophages. In order to follow these processes rapidly, the yeasts were labeled with Congo-red and their binding to the macrophages was measured spectrophotometrically after treatment with sodium dodecylsulfate. Phagocytosis was also followed by light microscopy. Binding of the yeasts was inhibited by about 80% after pretreating the macrophages with 150 micrograms/ml of WGA. This effect was reversed by subsequent incubation with N-acetyl-D-glucosamine, chitobiose or chitotriose, but was unaffected by methyl alpha-D-mannoside, N-acetyl-D-mannosamine, D-mannose or D-galactose. Pretreatment of the Congo-red yeasts with WGA did not inhibit their binding by the macrophages. Of a variety of lectins tested, only WGA and Datura stramonium lectin had this effect. Pretreating the macrophages with sialidase prevented the inhibition induced by WGA. Our findings suggest the presence on the macrophages of a class of WGA receptors not previously reported. 相似文献