全文获取类型
收费全文 | 72篇 |
免费 | 4篇 |
专业分类
76篇 |
出版年
2023年 | 1篇 |
2021年 | 1篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 1篇 |
2013年 | 8篇 |
2012年 | 9篇 |
2011年 | 5篇 |
2010年 | 2篇 |
2009年 | 3篇 |
2008年 | 2篇 |
2007年 | 1篇 |
2006年 | 1篇 |
2005年 | 5篇 |
2004年 | 1篇 |
2003年 | 6篇 |
2002年 | 3篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1984年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1970年 | 1篇 |
排序方式: 共有76条查询结果,搜索用时 15 毫秒
1.
T Steinkellner JW Yang TR Montgomery WQ Chen MT Winkler S Sucic G Lubec M Freissmuth Y Elgersma HH Sitte O Kudlacek 《The Journal of biological chemistry》2012,287(35):29627-29635
The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission, controlling the length and brevity of dopaminergic signaling. DAT is also the primary target of psychostimulant drugs such as cocaine and amphetamines. Conversely, methylphenidate and amphetamine are both used clinically in the treatment of attention-deficit hyperactivity disorder and narcolepsy. The action of amphetamines, which induce transport reversal, relies primarily on the ionic composition of the intra- and extracellular milieus. Recent findings suggest that DAT interacting proteins may also play a significant role in the modulation of reverse dopamine transport. The pharmacological inhibition of the serine/threonine kinase αCaMKII attenuates amphetamine-triggered DAT-mediated 1-methyl-4-phenylpyridinium (MPP(+)) efflux. More importantly, αCaMKII has also been shown to bind DAT in vitro and is therefore believed to be an important player within the DAT interactome. Herein, we show that αCaMKII co-immunoprecipitates with DAT in mouse striatal synaptosomes. Mice, which lack αCaMKII or which express a permanently self-inhibited αCaMKII (αCaMKII(T305D)), exhibit significantly reduced amphetamine-triggered DAT-mediated MPP(+) efflux. Additionally, we investigated mice that mimic a neurogenetic disease known as Angelman syndrome. These mice possess reduced αCaMKII activity. Angelman syndrome mice demonstrated an impaired DAT efflux function, which was comparable with that of the αCaMKII mutant mice, indicating that DAT-mediated dopaminergic signaling is affected in Angelman syndrome. 相似文献
2.
3.
Hideo Satsu Marie-Therese Schaeffer Miguel Guerrero Adrian Saldana Christina Eberhart Peter Hodder Charmagne Cayanan Stephan Schürer Barun Bhhatarai Ed Roberts Hugh Rosen Steven J. Brown 《Bioorganic & medicinal chemistry》2013,21(17):5373-5382
Molecular probe tool compounds for the Sphingosine 1-phosphate receptor 2 (S1PR2) are important for investigating the multiple biological processes in which the S1PR2 receptor has been implicated. Amongst these are NF-κB-mediated tumor cell survival and fibroblast chemotaxis to fibronectin. Here we report our efforts to identify selective chemical probes for S1PR2 and their characterization. We employed high throughput screening to identify two compounds which activate the S1PR2 receptor. SAR optimization led to compounds with high nanomolar potency. These compounds, XAX-162 and CYM-5520, are highly selective and do not activate other S1P receptors. Binding of CYM-5520 is not competitive with the antagonist JTE-013. Mutation of receptor residues responsible for binding to the zwitterionic headgroup of sphingosine 1-phosphate (S1P) abolishes S1P activation of the receptor, but not activation by CYM-5520. Competitive binding experiments with radiolabeled S1P demonstrate that CYM-5520 is an allosteric agonist and does not displace the native ligand. Computational modeling suggests that CYM-5520 binds lower in the orthosteric binding pocket, and that co-binding with S1P is energetically well tolerated. In summary, we have identified an allosteric S1PR2 selective agonist compound. 相似文献
4.
5.
6.
7.
Michael Liebrenz Marcel Schneider Anna Buadze Marie-Therese Gehring Anish Dube Carlo Caflisch 《PloS one》2015,10(11)
Background
High-dose benzodiazepine (BZD) dependence is associated with a wide variety of negative health consequences. Affected individuals are reported to suffer from severe mental disorders and are often unable to achieve long-term abstinence via recommended discontinuation strategies. Although it is increasingly understood that treatment interventions should take subjective experiences and beliefs into account, the perceptions of this group of individuals remain under-investigated.Methods
We conducted an exploratory qualitative study with 41 adult subjects meeting criteria for (high-dose) BZD-dependence, as defined by ICD-10. One-on-one in-depth interviews allowed for an exploration of this group’s views on the reasons behind their initial and then continued use of BZDs, as well as their procurement strategies. Mayring’s qualitative content analysis was used to evaluate our data.Results
In this sample, all participants had developed explanatory models for why they began using BZDs. We identified a multitude of reasons that we grouped into four broad categories, as explaining continued BZD use: (1) to cope with symptoms of psychological distress or mental disorder other than substance use, (2) to manage symptoms of physical or psychological discomfort associated with somatic disorder, (3) to alleviate symptoms of substance-related disorders, and (4) for recreational purposes, that is, sensation-seeking and other social reasons. Subjects often considered BZDs less dangerous than other substances and associated their use more often with harm reduction than as recreational. Specific obtainment strategies varied widely: the majority of participants oscillated between legal and illegal methods, often relying on the black market when faced with treatment termination.Conclusions
Irrespective of comorbidity, participants expressed a clear preference for medically related explanatory models for their BZD use. We therefore suggest that clinicians consider patients’ motives for long-term, high-dose BZD use when formulating treatment plans for this patient group, especially since it is known that individuals are more compliant with approaches they perceive to be manageable, tolerable, and effective. 相似文献8.
An alternative to radiation hybrid mapping for large-scale genome analysis in barley 总被引:3,自引:0,他引:3
Masoudi-Nejad A Nasuda S Bihoreau MT Waugh R Endo TR 《Molecular genetics and genomics : MGG》2005,274(6):589-594
The presence of a monosomic gametocidal chromosome (GC) in a barley chromosome addition line of common wheat generates structural
aberrations in the barley chromosome as well as in the wheat chromosomes of gametes lacking the GC. A collection of structurally
aberrant barley chromosomes is analogous to a panel of radiation hybrid (RH) mapping and is valuable for high-throughput physical
mapping. We developed 90 common wheat lines (GC lines) containing aberrant barley 7H chromosomes induced by a gametocidal
chromosome, 2C. DNAs isolated from these GC lines provided a panel of 7H chromosomal fragments in a wheat genetic background,
comparable with RH mapping panels in mammals. We used this 7H GC panel and the methodology for RH mapping to physically map
PCR-based barley markers, SSRs and AFLPs, onto chromosome 7H, relying on polymorphism between the 7H chromosome and the wheat
genome. We call this method GC mapping. This study describes a novel adaptation and combination of methods of inducing chromosomal
rearrangements to produce physical maps of markers. The advantages of the presented method are similar to RH mapping in that
non-polymorphic markers can be used and the mapping panels can be relatively easily obtained. In addition, mapping results
are cumulative when using the same mapping set with new markers. The GC lines will be available from the National Bioresources
Project-KOMUGI ().
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
9.
MacFadyen JR Haworth O Roberston D Hardie D Webster MT Morris HR Panico M Sutton-Smith M Dell A van der Geer P Wienke D Buckley CD Isacke CM 《FEBS letters》2005,579(12):2569-2575
Fibroblasts are a diverse cell type and display clear topographic differentiation and positional memory. In a screen for fibroblast specific markers we have characterized four monoclonal antibodies to endosialin (TEM1/CD248). Previous studies have reported that endosialin is a tumour endothelium marker and is localized intracellularly. We demonstrate conclusively that endosialin is a cell surface glycoprotein and is predominantly expressed by fibroblasts and a subset of pericytes associated with tumour vessels but not by tumour endothelium. These novel antibodies will facilitate the isolation and classification of fibroblast and pericyte lineages as well as the further functional analysis of endosialin. 相似文献
10.
Meiosis ensures the reduction of the genome before the formation of generative cells and promotes the exchange of genetic information between homologous chromosomes by recombination. Essential for these events are programmed DNA double strand breaks (DSBs) providing single-stranded DNA overhangs after their processing. These overhangs, together with the RADiation sensitive51 (RAD51) and DMC1 Disrupted Meiotic cDNA1 (DMC1) recombinases, mediate the search for homologous sequences. Current models propose that the two ends flanking a meiotic DSB have different fates during DNA repair, but the molecular details remained elusive. Here we present evidence, obtained in the model plant Arabidopsis thaliana, that the two recombinases, RAD51 and DMC1, localize to opposite sides of a meiotic DSB. We further demonstrate that the ATR kinase is involved in regulating DMC1 deposition at meiotic DSB sites, and that its elimination allows DMC1-mediated meiotic DSB repair even in the absence of RAD51. DMC1's ability to promote interhomolog DSB repair is not a property of the protein itself but the consequence of an ASYNAPTIC1 (Hop1)-mediated impediment for intersister repair. Taken together, these results demonstrate that DMC1 functions independently and spatially separated from RAD51 during meiosis and that ATR is an integral part of the regular meiotic program. 相似文献