全文获取类型
收费全文 | 83篇 |
免费 | 10篇 |
出版年
2019年 | 2篇 |
2018年 | 1篇 |
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 6篇 |
2013年 | 4篇 |
2012年 | 4篇 |
2011年 | 2篇 |
2010年 | 2篇 |
2009年 | 1篇 |
2008年 | 7篇 |
2007年 | 4篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 1篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有93条查询结果,搜索用时 406 毫秒
31.
Background
The taxonomic name of an organism is a key link between different databases that store information on that organism. However, in the absence of a single, comprehensive database of organism names, individual databases lack an easy means of checking the correctness of a name. Furthermore, the same organism may have more than one name, and the same name may apply to more than one organism. 相似文献32.
SMM?VerstappenEmail author AR?Poole M?Ionescu LE?King M?Abrahamowicz DM?Hofman JWJ?Bijlsma FPJG?Lafeber the Utrecht Rheumatoid Arthritis Cohort Study group 《Arthritis research & therapy》2005,8(1):R31
Introduction
The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA). 相似文献33.
Mercatante DR Bortner CD Cidlowski JA Kole R 《The Journal of biological chemistry》2001,276(19):16411-16417
There is ample evidence that deregulation of apoptosis results in the development, progression, and/or maintenance of cancer. Since many apoptotic regulatory genes (e.g. bcl-x) code for alternatively spliced protein variants with opposing functions, the manipulation of alternative splicing presents a unique way of regulating the apoptotic response. Here we have targeted oligonucleotides antisense to the 5'-splice site of bcl-x(L), an anti-apoptotic gene that is overexpressed in various cancers, and shifted the splicing pattern of Bcl-x pre-mRNA from Bcl-x(L) to Bcl-x(S), a pro-apoptotic splice variant. This approach induced significant apoptosis in PC-3 prostate cancer cells. In contrast, the same oligonucleotide treatment elicited a much weaker apoptotic response in MCF-7 breast cancer cells. Moreover, although the shift in Bcl-x pre-mRNA splicing inhibited colony formation in both cell lines, this effect was much less pronounced in MCF-7 cells. These differences in responses to oligonucleotide treatment were analyzed in the context of expression of Bcl-x(L), Bcl-x(S), and Bcl-2 proteins. The results indicate that despite the presence of Bcl-x pre-mRNA in a number of cell types, the effects of modification of its splicing by antisense oligonucleotides vary depending on the expression profile of the treated cells. 相似文献
34.
35.
Viktorian Miok Saskia M Wilting Mark A van de Wiel Annelieke Jaspers Paula I van Noort Ruud H Brakenhoff Peter JF Snijders Renske DM Steenbergen Wessel N van Wieringen 《BMC bioinformatics》2014,15(1)
Background
To determine which changes in the host cell genome are crucial for cervical carcinogenesis, a longitudinal in vitro model system of HPV-transformed keratinocytes was profiled in a genome-wide manner. Four cell lines affected with either HPV16 or HPV18 were assayed at 8 sequential time points for gene expression (mRNA) and gene copy number (DNA) using high-resolution microarrays. Available methods for temporal differential expression analysis are not designed for integrative genomic studies.Results
Here, we present a method that allows for the identification of differential gene expression associated with DNA copy number changes over time. The temporal variation in gene expression is described by a generalized linear mixed model employing low-rank thin-plate splines. Model parameters are estimated with an empirical Bayes procedure, which exploits integrated nested Laplace approximation for fast computation. Iteratively, posteriors of hyperparameters and model parameters are estimated. The empirical Bayes procedure shrinks multiple dispersion-related parameters. Shrinkage leads to more stable estimates of the model parameters, better control of false positives and improvement of reproducibility. In addition, to make estimates of the DNA copy number more stable, model parameters are also estimated in a multivariate way using triplets of features, imposing a spatial prior for the copy number effect.Conclusion
With the proposed method for analysis of time-course multilevel molecular data, more profound insight may be gained through the identification of temporal differential expression induced by DNA copy number abnormalities. In particular, in the analysis of an integrative oncogenomics study with a time-course set-up our method finds genes previously reported to be involved in cervical carcinogenesis. Furthermore, the proposed method yields improvements in sensitivity, specificity and reproducibility compared to existing methods. Finally, the proposed method is able to handle count (RNAseq) data from time course experiments as is shown on a real data set.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-327) contains supplementary material, which is available to authorized users. 相似文献36.
Lois A. Annab Carl D. Bortner Marie I. Sifre Jennifer M. Collins Ruchir R. Shah Darlene Dixon H. Karimi Kinyamu Trevor K. Archer 《Differentiation; research in biological diversity》2012
The heterogeneous nature of stem cells is an important issue in both research and therapeutic use in terms of directing cell lineage differentiation pathways, as well as self-renewal properties. Using flow cytometry we have identified two distinct subpopulations by size, large and small, within cultures of human embryonic stem (hES) cell lines. These two cell populations respond differentially to retinoic acid (RA) differentiation and several endocrine disruptor compounds (EDC). The large cell population responds to retinoic acid differentiation with greater than a 50% reduction in cell number and loss of Oct-4 expression, whereas the number of the small cell population does not change and Oct-4 protein expression is maintained. In addition, four estrogenic compounds altered SSEA-3 expression differentially between the two cell subpopulations changing their ratios relative to each other. Both populations express stem cell markers Oct-4, Nanog, Tra-1–60, Tra-1–80 and SSEA-4, but express low levels of differentiation markers common to the three germ layers. Cloning studies indicate that both populations can revive the parental population. Furthermore, whole genome microarray identified approximately 400 genes with significantly different expression between the two populations (p<0.01). We propose the differential response to RA in these populations is due to differential gene expression of Notch signaling members, CoupTF1 and CoupTF2, chromatin remodeling and histone modifying genes that render the small population resistant to RA differentiation. The findings that hES cells exist as heterogeneous populations with distinct responses to differentiation signals and environmental stimuli will be relevant for their use for drug discovery and disease therapy. 相似文献
37.
Ribosomal RNA secondary structure: compensatory mutations and implications for phylogenetic analysis 总被引:6,自引:0,他引:6
Using sequence data from the 28S ribosomal RNA (rRNA) genes of selected
vertebrates, we investigated the effects that constraints imposed by
secondary structure have on the phylogenetic analysis of rRNA sequence
data. Our analysis indicates that characters from both base-pairing regions
(stems) and non-base-pairing regions (loops) contain phylogenetic
information, as judged by the level of support of the phylogenetic results
compared with a well-established tree based on both morphological and
molecular data. The best results (the greatest level of support of
well-accepted nodes) were obtained when the complete data set was used.
However, some previously supported nodes were resolved using either the
stem or loop bases alone. Stem bases sustain a greater number of
compensatory mutations than would be expected at random, but the number is
< 40% of that expected under a hypothesis of perfect compensation to
maintain secondary structure. Therefore, we suggest that in phylogenetic
analyses, the weighting of stem characters be reduced by no more than 20%,
relative to that of loop characters. In contrast to previous suggestions,
we do not recommend weighting of stem positions by one-half, compared with
that of loop positions, because this overcompensates for the constraints
that selection imposes on the secondary structure of rRNA.
相似文献
38.
39.
Y T Kim S Tabor C Bortner J D Griffith C C Richardson 《The Journal of biological chemistry》1992,267(21):15022-15031
Bacteriophage T7 gene 2.5 protein has been purified to homogeneity from cells overexpressing its gene. Native gene 2.5 protein consists of a dimer of two identical subunits of molecular weight 25,562. Gene 2.5 protein binds specifically to single-stranded DNA with a stoichiometry of approximately 7 nucleotides bound per monomer of gene 2.5 protein; binding appears to be noncooperative. Electron microscopic analysis shows that gene 2.5 protein is able to disrupt the secondary structure of single-stranded DNA. The single-stranded DNA is extended into a chain of gene 2.5 protein dimers bound along the DNA. In fluorescence quenching and nitrocellulose filter binding assays, the binding constants of gene 2.5 protein to single-stranded DNA are 1.2 x 10(6) M-1 and 3.8 x 10(6) M-1, respectively. Escherichia coli single-stranded DNA-binding protein and phage T4 gene 32 protein bind to single-stranded DNA more tightly by a factor of 25. Fluorescence spectroscopy suggests that tyrosine residue(s), but not tryptophan residues, on gene 2.5 protein interacts with single-stranded DNA. 相似文献
40.
Rodrigo Franco Carl D. Bortner Ingo Schmitz John A. Cidlowski 《Apoptosis : an international journal on programmed cell death》2014,19(1):117-134
Glutathione (GSH) depletion is an important hallmark of apoptosis. We previously demonstrated that GSH depletion, by its efflux, regulates apoptosis by modulation of executioner caspase activity. However, both the molecular identity of the GSH transporter(s) involved and the signaling cascades regulating GSH loss remain obscure. We sought to determine the role of multidrug resistance protein 1 (MRP1) in GSH depletion and its regulatory role on extrinsic and intrinsic pathways of apoptosis. In human lymphoma cells, GSH depletion was stimulated rather than inhibited by pharmacological blockage of MRP1 with MK571. GSH loss was dependent on initiator caspases 8 and 9 activity. Genetic knock-down (>60 %) of MRP1 by stable transfection with short hairpin small interfering RNA significantly reduced MRP1 protein levels, which correlated directly with the loss of MRP1-mediated anion transport. However, GSH depletion and apoptosis induced by both extrinsic and intrinsic pathways were not affected by MRP1 knock-down. Interestingly, stimulation of GSH loss by MK571 also enhanced the initiator phase of apoptosis by stimulating initiator caspase 8 and 9 activity and pro-apoptotic BCL-2 interacting domain cleavage. Our results clearly show that caspase-dependent GSH loss and apoptosis are not mediated by MRP1 proteins and that GSH depletion stimulates the initiation phase of apoptosis in lymphoid cells. 相似文献