全文获取类型
收费全文 | 68篇 |
免费 | 11篇 |
出版年
2022年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 3篇 |
2013年 | 2篇 |
2012年 | 2篇 |
2011年 | 2篇 |
2010年 | 4篇 |
2009年 | 8篇 |
2008年 | 2篇 |
2007年 | 2篇 |
2006年 | 1篇 |
2005年 | 4篇 |
2004年 | 2篇 |
2003年 | 1篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1992年 | 1篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1975年 | 2篇 |
1967年 | 2篇 |
1961年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有79条查询结果,搜索用时 15 毫秒
51.
Optic nerve transection results in the death of retinal ganglion cells (RGCs) by apoptosis. Apoptosis is regulated by the Bcl-2 family of proteins, of which the Bcl-2 homology (BH3) -only proteins forms a subset. As BH3-only proteins have been shown to play a significant role in regulating cell death in the central nervous system, we wished to investigate the role of Bcl-2 interacting mediator of cell death (Bim), a prominent member of this protein family in the regulation of cell death in the RGC layer using in vitro retinal explants. In this study, we use an innovative retinal shaving procedure to isolate the cells of the ganglion cell layer to use for western blotting. Members of the BH3-only protein family are down-regulated during retinal development and are not normally expressed in the adult retina. Using this procedure, we demonstrate that Bim is re-expressed and its expression is increased over time following axotomy. Expression of Bad and Bik decreases over the same time course, whereas there is no indication that Bid and Puma are re-expressed. We show that explants from Bim knockout mice are resistant to axotomy-induced death when compared with their wild-type counterparts. Genetic deletion of Bim also prevents caspase 3 cleavage. The activity of Bim can be negatively regulated by phosphorylation. We show that the decrease of Bim phosphorylation correlates with a decrease in expression of survival kinases such as pAkt and pERK over the same time course. These results implicate Bim re-expression as being essential for axotomy-induced death of RGCs and that phosphorylation of Bim negatively regulates its activity in RGCs. 相似文献
52.
Background
Massive parallel sequencing is a powerful tool for variant discovery and genotyping. To reduce costs, sequencing of restriction enzyme based reduced representation libraries can be utilized. This technology is generally referred to as Genotyping By Sequencing (GBS). To deal with GBS experimental design and initial processing specific bioinformatic tools are needed.Results
GBSX is a package that assists in selecting the appropriate enzyme and the design of compatible in-line barcodes. Post sequencing, it performs optimized demultiplexing using these barcodes to create fastq files per barcode which can easily be plugged into existing variant analysis pipelines. Here we demonstrate the usability of the GBSX toolkit and demonstrate improved in-line barcode demultiplexing and trimming performance compared to existing tools.Conclusions
GBSX provides an easy to use suite of tools for designing and demultiplexing of GBS experiments. 相似文献53.
KJ Aufderheide 《Biotechnic & histochemistry》2016,91(5):352-356
The original ammoniacal silver carbonate staining technique and subsequent modification developed by Fernández-Galiano are useful for investigating ciliate protozoan systematics and/or ciliate cortical structure and morphogenesis. The technique is complicated, however, by both uncertainties arising from the need to count drops of reagents and subjective control of the staining intensity. I have resolved these complications by defining volumes of reagents rather than using drops and by defining a range of staining times. I also comment on various steps of the techniques. My techniques are simplified and refined to produce consistent, high quality staining results. 相似文献
54.
55.
Alena A. Antipova Tanya D. Sokolsky Christopher R. Clouser Eileen T. Dimalanta Cynthia L. Hendrickson Cisilya Kosnopo Clarence C. Lee Swati S. Ranade Lei Zhang Alan P. Blanchard Kevin J. McKernan 《Journal of biomolecular techniques》2009,20(5):253-257
Identifying genetic variants and mutations that underlie human diseases requires development of robust, cost-effective tools for routine resequencing of regions of interest in the human genome. Here, we demonstrate that coupling Applied Biosystems SOLiD™ system-sequencing platform with microarray capture of targeted regions provides an efficient and robust method for high-coverage resequencing and polymorphism discovery in human protein-coding exons. 相似文献
56.
Christina A. Bormann Chung Victoria L. Boyd Kevin J. McKernan Yutao Fu Cinna Monighetti Heather E. Peckham Melissa Barker 《PloS one》2010,5(2)
Methylation, the addition of methyl groups to cytosine (C), plays an important role in the regulation of gene expression in both normal and dysfunctional cells. During bisulfite conversion and subsequent PCR amplification, unmethylated Cs are converted into thymine (T), while methylated Cs will not be converted. Sequencing of this bisulfite-treated DNA permits the detection of methylation at specific sites. Through the introduction of next-generation sequencing technologies (NGS) simultaneous analysis of methylation motifs in multiple regions provides the opportunity for hypothesis-free study of the entire methylome. Here we present a whole methylome sequencing study that compares two different bisulfite conversion methods (in solution versus in gel), utilizing the high throughput of the SOLiD™ System. Advantages and disadvantages of the two different bisulfite conversion methods for constructing sequencing libraries are discussed. Furthermore, the application of the SOLiD™ bisulfite sequencing to larger and more complex genomes is shown with preliminary in silico created bisulfite converted reads. 相似文献
57.
58.
alpha4beta3delta GABA(A) receptors characterized by fluorescence resonance energy transfer-derived measurements of membrane potential 总被引:5,自引:0,他引:5
Adkins CE Pillai GV Kerby J Bonnert TP Haldon C McKernan RM Gonzalez JE Oades K Whiting PJ Simpson PB 《The Journal of biological chemistry》2001,276(42):38934-38939
Selective modulators of gamma-aminobutyric acid, type A (GABA(A)) receptors containing alpha(4) subunits may provide new treatments for epilepsy and premenstrual syndrome. Using mouse L(-tk) cells, we stably expressed the native GABA(A) receptor subunit combinations alpha(3)beta(3)gamma(2,) alpha(4)beta(3)gamma(2), and, for the first time, alpha(4)beta(3)delta and characterized their properties using a novel fluorescence resonance energy transfer assay of GABA-evoked depolarizations. GABA evoked concentration-dependent decreases in fluorescence resonance energy transfer that were blocked by GABA(A) receptor antagonists and, for alpha(3)beta(3)gamma(2) and alpha(4)beta(3)gamma(2) receptors, modulated by benzodiazepines with the expected subtype specificity. When combined with alpha(4) and beta(3), delta subunits, compared with gamma(2), conferred greater sensitivity to the agonists GABA, 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP), and muscimol and greater maximal efficacy to THIP. alpha(4)beta(3)delta responses were markedly modulated by steroids and anesthetics. Alphaxalone, pentobarbital, and pregnanolone were all 3-7-fold more efficacious at alpha(4)beta(3)delta compared with alpha(4)beta(3)gamma(2.) The fluorescence technique used in this study has proven valuable for extensive characterization of a novel GABA(A) receptor. For GABA(A) receptors containing alpha(4) subunits, our experiments reveal that inclusion of delta instead of gamma(2) subunits can increase the affinity and in some cases the efficacy of agonists and can increase the efficacy of allosteric modulators. Pregnanolone was a particularly efficacious modulator of alpha(4)beta(3)delta receptors, consistent with a central role for this subunit combination in premenstrual syndrome. 相似文献
59.
Mitchinson A Atack JR Blurton P Carling RW Castro JL Curley KS Russell MG Marshall G McKernan RM Moore KW Narquizian R Smith A Street LJ Thompson SA Wafford K 《Bioorganic & medicinal chemistry letters》2004,14(13):3441-3444
2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones are GABAA receptor benzodiazepine binding site ligands with functional selectivity for the alpha3 subtype over the alpha1 subtype. SAR studies to optimise this functional selectivity are described. 相似文献
60.
Claudia?Dumrese Christine?F?Maurus Daniel?Gygi M?rten?KJ?Schneider Michael?Walch Peter?Groscurth Urs?ZieglerEmail author 《BMC microbiology》2005,5(1):2