全文获取类型
收费全文 | 96篇 |
免费 | 8篇 |
出版年
2021年 | 3篇 |
2020年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2015年 | 6篇 |
2014年 | 3篇 |
2013年 | 2篇 |
2012年 | 4篇 |
2011年 | 5篇 |
2010年 | 3篇 |
2009年 | 2篇 |
2008年 | 2篇 |
2007年 | 5篇 |
2006年 | 3篇 |
2005年 | 8篇 |
2004年 | 7篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 10篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1977年 | 1篇 |
排序方式: 共有104条查询结果,搜索用时 937 毫秒
31.
32.
Sequence variations in small-subunit ribosomal RNAs of Hartmannella vermiformis and their phylogenetic implications 总被引:1,自引:0,他引:1
Evidence of associations between free-living amoebas and human disease has
been increasing in recent years. Knowledge about phylogenetic relationships
that may be important for the understanding of pathogenicity in the genera
involved is very limited at present. Consequently, we have begun to study
these relationships and report here on the phylogeny of Hartmannella
vermiformis, a free-living amoeba that can harbor the etiologic agent of
Legionnaires' disease. Our analysis is based on studies of small-subunit
ribosomal RNA genes (srDNA). Nucleotide sequences were determined for
nuclear srDNA from three strains of H. vermiformis isolated from the United
Kingdom, Germany, and the United States. These sequences then were compared
with a sequence previously obtained for a North American isolate by J. H.
Gunderson and M. L. Sogin. The four genes are 1,840 bp long, with an
average GC content of 49.6%. Sequence differences among the strains range
are 0.38%-0.76%. Variation occurs at 19 positions and includes 2
single-base indels plus 14 monotypic and 3 ditypic single-base
substitutions. Variation is limited to eight helix/loop structures
according to a current model for srRNA secondary structure. Parsimony,
distance, and bootstrap analyses used to examine phylogenetic relationships
between the srDNA sequences of H. vermiformis and other eukaryotes
indicated that Hartmannella sequences were most closely related to those of
Acanthamoeba and the alga Cryptomonas. All ditypic sites were consistent
with a separation between European and North American strains of
Hartmannella, but results of other tests of this relationship were
statistically inconclusive.
相似文献
33.
Cell-to-cell transfer of glial proteins to the squid giant axon: The glia- neuron protein transfer hypothesis
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The hypothesis that glial cells synthesize proteins which are transferred to adjacent neurons was evaluated in the giant fiber of the squid (Loligo pealei). When giant fibers are separated from their neuron cell bodies and incubated in the presence of radioactive amino acids, labeled proteins appear in the glial cells and axoplasm. Labeled axonal proteins were detected by three methods: extrusion of the axoplasm from the giant fiber, autoradiography, and perfusion of the giant fiber. This protein synthesis is completely inhibited by puromycin but is not affected by chloramphenicol. The following evidence indicates that the labeled axonal proteins are not synthesized within the axon itself. (a) The axon does not contain a significant amount of ribosomes or ribosomal RNA. (b) Isolated axoplasm did not incorporate [(3)H]leucine into proteins. (c) Injection of Rnase into the giant axon did not reduce the appearance of newly synthesized proteins in the axoplasm of the giant fiber. These findings, coupled with other evidence, have led us to conclude that the adaxonal glial cells synthesize a class of proteins which are transferred to the giant axon. Analysis of the kinetics of this phenomenon indicates that some proteins are transferred to the axon within minutes of their synthesis in the glial cells. One or more of the steps in the transfer process appear to involve Ca++, since replacement of extracellular Ca++ by either Mg++ or Co++ significantly reduces the appearance of labeled proteins in the axon. A substantial fraction of newly synthesized glial proteins, possibly as much as 40 percent, are transferred to the giant axon. These proteins are heterogeneous and range in size from 12,000 to greater than 200,000 daltons. Comparisons of the amount of amino acid incorporation in glia cells and neuron cell bodies raise the possibility that the adaxonal glial cells may provide an important source of axonal proteins which is supplemental to that provided by axonal transport from the cell body. These findings are discussed with reference to a possible trophic effect of glia on neurons and metabolic cooperation between adaxonal glia and the axon. 相似文献
34.
Background
The reliability of whole-genome prediction models (WGP) based on using high-density single nucleotide polymorphism (SNP) panels critically depends on proper specification of key hyperparameters. A currently popular WGP model labeled BayesB specifies a hyperparameter π, that is `loosely used to describe the proportion of SNPs that are in linkage disequilibrium (LD) with causal variants. The remaining markers are specified to be random draws from a Student t distribution with key hyperparameters being degrees of freedom v and scale s2.Methods
We consider three alternative Markov chain Monte Carlo (MCMC) approaches based on the use of Metropolis-Hastings (MH) to estimate these key hyperparameters. The first approach, termed DFMH, is based on a previously published strategy for which s2 is drawn by a Gibbs step and v is drawn by a MH step. The second strategy, termed UNIMH, substitutes MH for Gibbs when drawing s2 and further collapses or marginalizes the full conditional density of v. The third strategy, termed BIVMH, is based on jointly drawing the two hyperparameters in a bivariate MH step. We also tested the effect of misspecification of s2 for its effect on accuracy of genomic estimated breeding values (GEBV), yet allowing for inference on the other hyperparameters.Results
The UNIMH and BIVMH strategies had significantly greater (P < 0.05) computational efficiencies for estimating v and s2 than DFMH in BayesA (π = 1) and BayesB implementations. We drew similar conclusions based on an analysis of the public domain heterogeneous stock mice data. We also determined significant drops (P < 0.01) in accuracies of GEBV under BayesA by overspecifying s2, whereas BayesB was more robust to such misspecifications. However, understating s2 was compensated by counterbalancing inferences on v in BayesA and BayesB, and on π in BayesB.Conclusions
Sampling strategies based solely on MH updates of v and s2, and collapsed representations of full conditional densities can improve the computational efficiency of MCMC relative to the use of Gibbs updates. We believe that proper inferences on s2, v and π are vital to ensure that the accuracy of GEBV is maximized when using parametric WGP models.Electronic supplementary material
The online version of this article (doi:10.1186/s12711-015-0092-x) contains supplementary material, which is available to authorized users. 相似文献35.
Annelot F. Schoffelen Annemarie M. J. Wensing Hugo A. Tempelman Sibyl P. M. Geelen Andy I. M. Hoepelman Roos E. Barth 《PloS one》2013,8(3)
Objective
This study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa.Methods
An observational cohort study was performed on 210 patients (including 39 children) who initiated PI-based second-line therapy at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (plasma HIV-1 RNA<400 copies/ml), full virological suppression (plasma HIV-1 RNA<50 copies/ml) and treatment failure (virological failure (plasma HIV-1 RNA>1000 after initial virological response) or on-going viremia (plasma HIV-1 RNA never<400 copies/ml for more than six months)). Data were analyzed by an on-treatment (OT) and intention-to-treat (ITT) approach. Analyses were primarily performed on the group of patients who switched following first-line virological failure.Results
Median duration of follow-up after switch to second-line treatment was 20 months [IQR 11–35]. 191 patients had switched to second-line ART due to first-line virological failure. 139/191 of them (72.8%, ITT) were in care and on treatment at the end of follow-up and 11/191 (5.8%, ITT) had died. After twelve months, an adequate virological response was seen in 92/128 patients (71.9%, OT), of which 78/128 (60.9%, OT) experienced full virological suppression. Virological response remained stable after 24 months. Virological efficacy was similar amongst adult and pediatric patients. As in first-line ART, we observed a lack of correlation between virological failure and WHO-defined immunological failure.Conclusions
Good virological outcomes following first-line failure can be achieved with PI-based, second-line antiretroviral therapy in both adult and pediatric patients in rural South Africa. Retention rates were high and virological outcomes were sustainable during the two-year follow-up period, although persisting low-level viremia occurred in a subset of patients. The observed viro-immunological dissociation emphasizes the need for virological monitoring. 相似文献36.
Pauline?AaltenEmail author Inez?HGB?Ramakers Geert?Jan?Biessels Peter?Paul?de Deyn Huiberdina?L?Koek Marcel?GM?OldeRikkert Ania?M?Oleksik Edo?Richard Lieke?L?Smits John?C?van Swieten Laura?K?Teune Aad?van der Lugt Frederik?Barkhof Charlotte?E?Teunissen Nico?Rozendaal Frans?RJ?Verhey Wiesje?M?van der Flier 《BMC neurology》2014,14(1):254
37.
38.
39.
40.