全文获取类型
收费全文 | 145篇 |
免费 | 14篇 |
出版年
2021年 | 3篇 |
2018年 | 3篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 4篇 |
2014年 | 6篇 |
2013年 | 9篇 |
2012年 | 6篇 |
2011年 | 10篇 |
2010年 | 4篇 |
2009年 | 7篇 |
2008年 | 4篇 |
2007年 | 11篇 |
2006年 | 3篇 |
2005年 | 7篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 2篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1964年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1955年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有159条查询结果,搜索用时 15 毫秒
111.
Acute and persistent infection of human neural cell lines by human coronavirus OC43 总被引:4,自引:0,他引:4 下载免费PDF全文
Human coronaviruses (HuCV) are recognized respiratory pathogens. Data accumulated by different laboratories suggest their neurotropic potential. For example, primary cultures of human astrocytes and microglia were shown to be susceptible to an infection by the OC43 strain of HuCV (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800-806, 1997). We speculate that the neurotropism of HuCV will lead to persistence within the central nervous system, as was observed for murine coronaviruses. As a first step in the verification of our hypothesis, we have characterized the susceptibility of various human neural cell lines to infection by HuCV-OC43. Viral antigen, infectious virus progeny, and viral RNA were monitored during both acute and persistent infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK-N-SH, neuroglioma H4, oligodendrocytic MO3.13, and the CHME-5 immortalized fetal microglial cell lines, were all susceptible to an acute infection by HuCV-OC43. Viral antigen and RNA and release of infectious virions were observed during persistent HuCV-OC43 infections ( approximately 130 days of culture) of U-87 MG, U-373 MG, MO3.13, and H4 cell lines. Nucleotide sequences of RNA encoding the putatively hypervariable viral S1 gene fragment obtained after 130 days of culture were compared to that of initial virus input. Point mutations leading to amino acid changes were observed in all persistently infected cell lines. Moreover, an in-frame deletion was also observed in persistently infected H4 cells. Some point mutations were observed in some molecular clones but not all, suggesting evolution of the viral population and the emergence of viral quasispecies during persistent infection of H4, U-87 MG, and MO3.13 cell lines. These results are consistent with the potential persistence of HuCV-OC43 in cells of the human nervous system, accompanied by the production of infectious virions and molecular variation of viral genomic RNA. 相似文献
112.
Construction of Defined Human Engineered Cardiac Tissues to Study Mechanisms of Cardiac Cell Therapy
Timothy J. Cashman Rebecca Josowitz Bruce D. Gelb Ronald A. Li Nicole C. Dubois Kevin D. Costa 《Journal of visualized experiments : JoVE》2016,(109)
Human cardiac tissue engineering can fundamentally impact therapeutic discovery through the development of new species-specific screening systems that replicate the biofidelity of three-dimensional native human myocardium, while also enabling a controlled level of biological complexity, and allowing non-destructive longitudinal monitoring of tissue contractile function. Initially, human engineered cardiac tissues (hECT) were created using the entire cell population obtained from directed differentiation of human pluripotent stem cells, which typically yielded less than 50% cardiomyocytes. However, to create reliable predictive models of human myocardium, and to elucidate mechanisms of heterocellular interaction, it is essential to accurately control the biological composition in engineered tissues. To address this limitation, we utilize live cell sorting for the cardiac surface marker SIRPα and the fibroblast marker CD90 to create tissues containing a 3:1 ratio of these cell types, respectively, that are then mixed together and added to a collagen-based matrix solution. Resulting hECTs are, thus, completely defined in both their cellular and extracellular matrix composition.Here we describe the construction of defined hECTs as a model system to understand mechanisms of cell-cell interactions in cell therapies, using an example of human bone marrow-derived mesenchymal stem cells (hMSC) that are currently being used in human clinical trials. The defined tissue composition is imperative to understand how the hMSCs may be interacting with the endogenous cardiac cell types to enhance tissue function. A bioreactor system is also described that simultaneously cultures six hECTs in parallel, permitting more efficient use of the cells after sorting. 相似文献
113.
N R Cashman 《CMAJ》1997,157(10):1381-1385
By biological and medical criteria, prions are infectious agents; however, many of their properties differ profoundly from those of conventional microbes. Prions are "encoded" by alterations in protein conformation rather than in nucleic acid or amino acid sequence. New epidemic prion diseases (bovine spongiform encephalopathy and new variant Creutzfeldt-Jakob disease) have recently emerged under the active surveillance of the modern world. The risk of contracting prion disease from blood products or other biologicals is now a focus of worldwide concern. Much has been discovered about prions and prion diseases, but much remains to be done. 相似文献
114.
An anchored restriction-mapping approach applied to the genetic analysis of the Anopheles gambiae malaria vector complex 1 总被引:1,自引:0,他引:1
We introduce here a simple approach for rapidly determining restriction
maps for a number of regions of a genome; this involves "anchoring" a map
with a rare restriction site (in this case the seldom-cutting EagI)
followed by partial digestion of a frequent-cutting enzyme (e.g., Sau 3A).
We applied this technology to five species of the Anopheles gambiae
complex. In a single Southern blot we obtained about a 15-kb restriction
map each for the mtDNA, rRNA gene, and a scnDNA region for each of five
species. Phylogenetic analyses of these regions yield trees at odds with
the more traditional chromosome inversion-based trees. The value of the
approach for systematic purposes is the ease with which several large,
independent regions of the genome can be quickly assayed for molecular
variation.
相似文献
115.
B A Gould H A Kieso R Hornung D G Altman P M Cashman E B Raftery 《BMJ (Clinical research ed.)》1982,285(6356):1691-1694
Self-recording of the blood pressure by patients away from hospital or office ("home blood pressure") has been advocated as providing a better estimate of "true" blood pressure. The reliability of home blood-pressure recording has been assessed only by standard indirect methods which themselves are subject to considerable error and variability. The accuracy of self-recorded blood pressures was therefore assessed in 57 patients with essential hypertension by comparison with simultaneous measurements of clinic blood pressures and with intra-arterial blood pressures recorded at home and at hospital. Home systolic blood pressures showed good agreement with clinic and intra-arterial pressures, but home diastolic blood pressures overestimated intra-arterial pressures, as did clinic diastolic pressures. The clinic and home diastolic pressures showed good agreement. There was considerable variability in individual differences comparing the indirect and intra-arterial methods, though the two indirect methods showed much closer agreement. This study suggests that home blood pressures are as accurate as clinic readings but may be recorded more frequently and thus provide more useful information. Neither is likely to approximate the intra-arterial blood pressure. 相似文献
116.
N-terminus determination: FAD and NADP binding domain mapping of hog liver flavin-containing monooxygenase by tandem mass spectrometry 总被引:1,自引:0,他引:1
S H Guan A M Falick J R Cashman 《Biochemical and biophysical research communications》1990,170(2):937-943
Highly purified hog liver flavin-containing monooxygenase was sequentially denatured, reduced, carboxymethylated, and digested with endoproteinase Glu-C. The purified peptides were subjected to mass spectrometric analysis and the amino acid sequence of selected fragments was determined by tandem mass spectrometry. The amino acid sequence of the first 12 residues of the N-terminus was: Ac-Ala-Lys-Arg-Val-Ala-Ile-Val-Gly-Ala-Gly-Val-Ser-Gly. The amino acid sequence determined for another peptide was: Lys-Ser-Val-Leu-Val-Val-Gly-Met-Gly-Asn-Ser-Gly-Thr-Asp-Ile-Ala-Val-Glu. The results provide direct evidence for the structure of the N-terminal modification of the protein and for the existence of the FAD and NADP binding domains of Gly-X-Gly-X-X-Gly. 相似文献
117.
118.
Rakhit R Robertson J Vande Velde C Horne P Ruth DM Griffin J Cleveland DW Cashman NR Chakrabartty A 《Nature medicine》2007,13(6):754-759
Misfolding of Cu/Zn-superoxide dismutase (SOD1) is emerging as a mechanism underlying motor neuron degeneration in individuals with amyotrophic lateral sclerosis (ALS) who carry a mutant SOD1 gene (SOD1 ALS). Here we describe a structure-guided approach to developing an antibody that specifically recognizes monomer-misfolded forms of SOD1. We raised this antibody to an epitope that is normally buried in the SOD1 native homodimer interface. The SOD1 exposed dimer interface (SEDI) antibody recognizes only those SOD1 conformations in which the native dimer is disrupted or misfolded and thereby exposes the hydrophobic dimer interface. Using the SEDI antibody, we established the presence of monomer-misfolded SOD1 in three ALS mouse models, with G37R, G85R and G93A SOD1 mutations, and in a human individual with an A4V SOD1 mutation. Despite ubiquitous expression, misfolded SOD1 was found primarily within degenerating motor neurons. Misfolded SOD1 appeared before the onset of symptoms and decreased at the end stage of the disease, concomitant with motor neuron loss. 相似文献
119.