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1.
    

Background  

a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed.  相似文献   
2.
  总被引:8,自引:0,他引:8  
We have examined the phylogenetic distribution of two t-specific markersamong representatives of various taxa belonging to the genus Mus. Thecentromeric TCP-1a marker (a testicular protein variant specific for allt-haplotypes so far studied) has also been apparently detected in severalnon-t representatives of the Mus IVA, Mus IVB, and probably M. cervicolorspecies. By contrast, a t-specific restriction- fragment-lengthpolymorphism allele (RFLP) of the telomeric alpha- globin pseudogene DNAmarker alpha-psi-4 was found only in animals belonging to the M.musculus-complex species either bearing genuine t- haplotypes or, like theM. m. bactrianus specimen studied here, likely to do so. This t-specificalpha-psi-4 RFLP allele was found to be as divergent from the RFLP allelesof the latter, non-t, taxonomical groups as it is from Mus 4A, Mus 4B, orM. spretus ones. These results suggest the presence of t-haplotypes and oft-specific markers in populations other than those belonging to the M. m.domesticus and M. m. musculus subspecies, implying a possible origin fort-haplotypes prior to the radiation of the most recent offshoot of the Musgenus (i.e., the spretus/domesticus divergence), some 1-3 Myr ago.  相似文献   
3.
    
Substitute methadone prescribing is one of the main modes of treatment for opiate dependence. This study examined the relationship between methadone dose (measured by daily dose and methadone's active (R)‐enantiomer blood levels) and opiate receptor function. Nine subjects on substitute methadone (30‐90 mg daily) received three subcutaneous injections 1.5 hours apart (saline, 5 mg and 10 mg hydromorphone, a short‐acting opiate agonist) followed by measures of functional response in particular saccadic eye movements (SEMs), as well as self‐report measures. Ten mg of hydromorphone significantly slowed SEM parameters (peak velocity by 15%, p <0.005; peak acceleration by 20%, p <0.025; peak deceleration by 26%, p <0.025) and the SEM velocity changes correlated significantly with (R)‐methadone levels (r =0.844, p <0.005) and with the oral dose of methadone being taken (r =0.829, p <0.005). Although a similar trend was observed for 5 mg, this was not significant. These finding suggest that, at higher methadone doses (resulting in higher plasma concentrations), there is significant tolerance to the action of agonists. Such studies may help in refining our understanding of the actions of methadone and the SEM measure could help in defining the degree of tolerance in individuals using street heroin.  相似文献   
4.

Background

In translational cancer research, gene expression data is collected together with clinical data and genomic data arising from other chip based high throughput technologies. Software tools for the joint analysis of such high dimensional data sets together with clinical data are required.

Results

We have developed an open source software tool which provides interactive visualization capability for the integrated analysis of high-dimensional gene expression data together with associated clinical data, array CGH data and SNP array data. The different data types are organized by a comprehensive data manager. Interactive tools are provided for all graphics: heatmaps, dendrograms, barcharts, histograms, eventcharts and a chromosome browser, which displays genetic variations along the genome. All graphics are dynamic and fully linked so that any object selected in a graphic will be highlighted in all other graphics. For exploratory data analysis the software provides unsupervised data analytics like clustering, seriation algorithms and biclustering algorithms.

Conclusions

The SEURAT software meets the growing needs of researchers to perform joint analysis of gene expression, genomical and clinical data.  相似文献   
5.
  总被引:3,自引:1,他引:3  
The results described in the accompanying article support the model inwhich glucosylphosphoryldolichol (Glc-P-Dol) is synthesized on thecytoplasmic face of the ER, and functions as a glucosyl donor for threeGlc-P-Dol:Glc0-2Man9-GlcNAc2-P-P-Dol glucosyltransferases (GlcTases) in thelumenal compartment. In this study, the enzymatic synthesis and structuralcharacterization by NMR and electrospray-ionization tandem massspectrometry of a series of water-soluble beta-Glc-P-Dol analogs containing2-4 isoprene units with either the cis - or trans - stereoconfiguration inthe beta-position are described. The water- soluble analogs were (1) usedto examine the stereospecificity of the Glc-P-Dol:Glc0-2Man9GlcNAc2-P-P-Dolglucosyltransferases (GlcTases) and (2) tested as potential substrates fora membrane protein(s) mediating the transbilayer movement of Glc-P-Dol insealed ER vesicles from rat liver and pig brain. The Glc-P-Dol-mediatedGlcTases in pig brain microsomes utilized [3H]Glc-labeled Glc-P-Dol10,Glc-P-(omega, c )Dol15, Glc-P(omega, t,t )Dol20, and Glc-P-(omega, t,c)Dol20as glucosyl donors with [3H]Glc3Man9GlcNAc2-P-P-Dol the major productlabeled in vitro. A preference was exhibited for C15-20 substratescontaining an internal cis -isoprene unit in the beta-position. Inaddition, the water-soluble analog, Glc-P-Dol10, was shown to enter thelumenal compartment of sealed microsomal vesicles from rat liver and pigbrain via a protein-mediated transport system enriched in the ER. Theproperties of the ER transport system have been characterized. Glc-P-Dol10was not transported into or adsorbed by synthetic PC-liposomes orbovine erythrocytes. The results of these studies indicate that (1) theinternal cis -isoprene units are important for the utilization of Glc-P-Dolas a glucosyl donor and (2) the transport of the water- soluble analog mayprovide an experimental approach to assay the hypothetical \"flippase\"proposed to mediate the transbilayer movement of Glc-P-Dol from thecytoplasmic face of the ER to the lumenal monolayer.  相似文献   
6.
    
The annual cycle of physical and chemical variables and plankton dynamics was studied in two shallow ponds (East and West Ponds) of the El Hondo wetland, an ecosystem of international importance. Water conductivity increased up to 31–49 mS cm–1 as water level decreased due to high evaporation and minimal water inputs. Initially considered mesohaline, the waters were reclassified as polyhaline during the hot season. EP was subject to successive desiccation‐flooding cycles, and flooding of the dried sediment caused the release of high concentrations of nitrogen and phosphorus compounds, which quickly depleted. The algal species composition was typical of eutrophic ecosystems, and the chlorophyll content indicated that EP was eutrophic and WP mesotrophic. Phytoplanktonic species richness and diversity were low in both ponds. Algal assemblages, in terms of biovolume, were mainly dominated by Dinophyceae in EP and by Cryptophyta in WP. The zooplankton community was dominated by Rotifers (Brachionus and Hexarthra), although Copepods and Ciliates were also important. Different water inputs to the ponds, partial drying in EP during the warm season with the subsequent higher increment of salinity, and the presence of dense populations of submerged macrophytes in WP, explain the differences in plankton communities found between the two ponds.  相似文献   
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9.
    
Mesenchymal stem cells (MSCs) have received significant attention in recent years due to their large potential for cell therapy. Indeed, they secrete a wide variety of immunomodulatory factors of interest for the treatment of immune-related disorders and inflammatory diseases. MSCs can be extracted from multiple tissues of the human body. However, several factors may restrict their use for clinical applications: the requirement of invasive procedures for their isolation, their limited numbers, and their heterogeneity according to the tissue of origin or donor. In addition, MSCs often present early signs of replicative senescence limiting their expansion in vitro, and their therapeutic capacity in vivo. Due to the clinical potential of MSCs, a considerable number of methods to differentiate induced pluripotent stem cells (iPSCs) into MSCs have emerged. iPSCs represent a new reliable, unlimited source to generate MSCs (MSCs derived from iPSC, iMSCs) from homogeneous and well-characterized cell lines, which would relieve many of the above mentioned technical and biological limitations. Additionally, the use of iPSCs prevents some of the ethical concerns surrounding the use of human embryonic stem cells. In this review, we analyze the main current protocols used to differentiate human iPSCs into MSCs, which we classify into five different categories: MSC Switch, Embryoid Body Formation, Specific Differentiation, Pathway Inhibitor, and Platelet Lysate. We also evaluate common and method-specific culture components and provide a list of positive and negative markers for MSC characterization. Further guidance on material requirements to produce iMSCs with these methods and on the phenotypic features of the iMSCs obtained is added. The information may help researchers identify protocol options to design and/or refine standardized procedures for large-scale production of iMSCs fitting clinical demands.  相似文献   
10.
    
Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects.  相似文献   
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