全文获取类型
收费全文 | 128篇 |
免费 | 10篇 |
专业分类
138篇 |
出版年
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2016年 | 3篇 |
2015年 | 5篇 |
2014年 | 8篇 |
2013年 | 8篇 |
2012年 | 8篇 |
2011年 | 2篇 |
2010年 | 7篇 |
2009年 | 4篇 |
2008年 | 7篇 |
2007年 | 3篇 |
2006年 | 5篇 |
2005年 | 2篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1978年 | 3篇 |
1975年 | 1篇 |
1972年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有138条查询结果,搜索用时 0 毫秒
21.
William C. Reid Rafael Casas Georgios Z. Papadakis Siva Muthusamy Dianne E. Lee Wael G. Ibrahim Anand Nair Deloris Koziol Dragan Maric Dima A. Hammoud 《PloS one》2016,11(3)
Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era. 相似文献
22.
Higher‐order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle 下载免费PDF全文
Arjen J Jakobi Abul K Tarafder Yury S Bykov Andrea Picco Wanda Kukulski Jan Kosinski Wim JH Hagen Arvind C Ravichandran Matthias Wilmanns Marko Kaksonen John AG Briggs Carsten Sachse 《EMBO reports》2016,17(7):1044-1060
Selective autophagy is the mechanism by which large cargos are specifically sequestered for degradation. The structural details of cargo and receptor assembly giving rise to autophagic vesicles remain to be elucidated. We utilize the yeast cytoplasm‐to‐vacuole targeting (Cvt) pathway, a prototype of selective autophagy, together with a multi‐scale analysis approach to study the molecular structure of Cvt vesicles. We report the oligomeric nature of the major Cvt cargo Ape1 with a combined 2.8 Å X‐ray and negative stain EM structure, as well as the secondary cargo Ams1 with a 6.3 Å cryo‐EM structure. We show that the major dodecameric cargo prApe1 exhibits a tendency to form higher‐order chain structures that are broken upon interaction with the receptor Atg19 in vitro. The stoichiometry of these cargo–receptor complexes is key to maintaining the size of the Cvt aggregate in vivo. Using correlative light and electron microscopy, we further visualize key stages of Cvt vesicle biogenesis. Our findings suggest that Atg19 interaction limits Ape1 aggregate size while serving as a vehicle for vacuolar delivery of tetrameric Ams1. 相似文献
23.
Sarita AY Hartgring Cynthia R Willis Johannes WJ Bijlsma Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2012,14(3):R137
Introduction
We sought to investigate the capacity of interleukin (IL)-7 to enhance collagen-induced arthritis and to study by what mechanisms this is achieved.Methods
Mice received multiple injections with IL-7 or phosphate-buffered saline (PBS) as a control. Arthritis severity and incidence were determined by visual examination of the paws. Joint destruction was determined by assessing radiographs and immunohistochemistry of the ankle joints. Total cellularity and numbers of T-cell and B-cell subsets were assessed, as well as ex vivo production of interferon-γ (IFN-γ), IL-17, and IL-4. Proinflammatory mediators were measured in serum with multianalyte profiling.Results
IL-7 increased arthritis severity and radiology-assessed joint destruction. This was consistent with IL-7-increased intensity of cell infiltrates, bone erosions, and cartilage damage. Splenic CD19+ B cells and CD19+/GL7+ germinal center B cells, as well as CD4 and CD8 numbers, were increased by IL-7. IL-7 expanded memory T cells, associated with increased percentages of IFN-γ-, IL-4-, and IL-17-producing CD4+ T cells. On antigen restimulation of draining lymph node cells in vitro IL-7 treatment was found to increase IFN-γ and IL-17 production, whereas IL-4 was reduced. IL-7 also increased concentrations of proinflammatory mediators, indicative of T-cell activation (sCD40L), vascular activation (VCAM-1, VEGF), tissue destruction (fibroblast growth factor-basic (FGF-b), LIF), and chemotaxis (MIP-1γ, MIP-3β, lymphotactin, MDC, and MCP-5).Conclusions
In arthritic mice, IL-7 causes expansion of T and B cells, associated with increased levels of proinflammatory mediators. IL-7 intensifies arthritis severity and joint destruction, accompanied by increased Th1 and Th17 activity. These data indicate that IL-7 could be an important mediator in arthritic conditions and that targeting IL-7 or its receptor represent novel therapeutic strategies. 相似文献24.
Soil microbial communities can have an important role in the adaptation of plants to their local abiotic soil conditions and in mediating plant responses to environmental stress. This has been clearly demonstrated for individual plant species, but it is unknown how locally adapted microbes may affect plant communities. It is possible that the adaptation of microbial communities to local conditions can shape plant community composition. Additionally, it is possible that the effects of locally adapted microorganisms on individual plant species could be altered by co-occurring plant species. We tested these possibilities in plant community mesocosms with soils and mycorrhizal fungi (AMF) from three locations. We found that plant community biomass responded positively to local adaptation of AMF to soil conditions. Plant community composition also changed in response to local adaptation of AMF. Unexpectedly, the strongest benefits of locally adapted AMF went to early successional plant species that have the highest relative growth rates and the lowest responsiveness to the presence of AMF. Late successional plants that responded positively overall to the presence of AMF were often suppressed in communities with local AMF, perhaps because of strong competition from fast growing plant species. These results show that local adaptation of soil microbial communities can shape plant community composition, and the benefits that plants derive from locally adapted microorganisms can be reshaped by the competitive context in which these associations occur. 相似文献
25.
26.
A homologous family of UDP- N -acetylgalactosamine: polypeptide N -
acetylgalactosaminyltransferases (GalNAc-transferases) initiate O-
glycosylation. These transferases share overall amino acid sequence
similarities of approximately 45-50%, but segments with higher similarities
of approximately 80% are found in the putative catalytic domain. Here we
have characterized the genomic organization of the coding regions of three
GalNAc-transferase genes and determined their chromosomal localization. The
coding regions of GALNT1 , -T2 , and -T3 were found to span 11, 16, and 10
exons, respectively. Several intron/exon boundaries were conserved within
the three genes. One conserved boundary was shared in a homologous C.
elegans GalNAc- transferase gene. Fluorescence in situ hybridization showed
that GALNT1 , -T2 , and -T3 are localized at chromosomes 18q12-q21,
1q41-q42, and 2q24-q31, respectively. These results suggest that the
members of the polypeptide GalNAc-transferase family diverged early in
evolution from a common ancestral gene through gene duplication.
相似文献
27.
J. A. Koziol 《Biometrical journal. Biometrische Zeitschrift》1988,30(7):787-793
We describe orthogonal components in multivariate analysis of variance, and illustrate their value when assessing restricted alternatives. 相似文献
28.
29.
Reixach N Adamski-Werner SL Kelly JW Koziol J Buxbaum JN 《Biochemical and biophysical research communications》2006,348(3):889-897
The amyloidoses are the extracellular subset of a group of diseases in which in vivo protein misfolding leads to a pathologic gain of function, i.e., aggregation leading to protein deposition, with subsequent tissue damage. Wild-type and mutant transthyretins (TTR) are the etiologic agents in prototypic systemic amyloidoses. We describe a cell-based assay that measures the cytotoxicity of physiologic concentrations of the amyloidogenic Val30Met TTR variant (V30M TTR) using cells of the same lineage as the in vivo tissue target of amyloid deposition. We have utilized the assay to screen small molecules for their capacity to inhibit the TTR-induced cell damage. We compared the inhibitory activity of each compound with its ability to prevent TTR fibril formation in vitro. Our results emphasize the importance of screening compounds under physiologic conditions. Moreover, if a common conformational intermediate is responsible for cell death in all the amyloid diseases, the cell-based assay has the potential to aid in the discovery of compounds useful in the treatment of amyloidoses caused by other misfolded proteins as well as those caused by TTR. 相似文献
30.
Koziol JA Feng AC Jia Z Wang Y Goodison S McClelland M Mercola D 《Bioinformatics (Oxford, England)》2009,25(1):54-60
MOTIVATION: Classification and regression trees have long been used for cancer diagnosis and prognosis. Nevertheless, instability and variable selection bias, as well as overfitting, are well-known problems of tree-based methods. In this article, we investigate whether ensemble tree classifiers can ameliorate these difficulties, using data from two recent studies of radical prostatectomy in prostate cancer. RESULTS: Using time to progression following prostatectomy as the relevant clinical endpoint, we found that ensemble tree classifiers robustly and reproducibly identified three subgroups of patients in the two clinical datasets: non-progressors, early progressors and late progressors. Moreover, the consensus classifications were independent predictors of time to progression compared to known clinical prognostic factors. 相似文献