全文获取类型
收费全文 | 73篇 |
免费 | 5篇 |
出版年
2021年 | 3篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 1篇 |
2013年 | 3篇 |
2012年 | 3篇 |
2011年 | 7篇 |
2009年 | 3篇 |
2008年 | 2篇 |
2007年 | 3篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1954年 | 2篇 |
1952年 | 1篇 |
排序方式: 共有78条查询结果,搜索用时 31 毫秒
71.
Appleyard AN Herbert RB Henderson PJ Watts A Spooner PJ 《Biochimica et biophysica acta》2000,1509(1-2):55-64
The binding of the transport inhibitor forskolin, synthetically labelled with (13)C, to the galactose-H(+) symport protein GalP, overexpressed in its native inner membranes from Escherichia coli, was studied using cross-polarization magic angle spinning (13)C NMR. (13)C-Labelled D-galactose and D-glucose were displaced from GalP with the singly labelled [7-OCO(13)CH(3)]forskolin and were not bound to any alternative site within the protein, demonstrating that any multiple sugar binding sites are not simultaneously accessible to these sugars and the inhibitor within GalP. The observation of singly (13)C-labelled forskolin was hampered by interference from natural abundance (13)C in the membranes and so the effectiveness of double-quantum filtration was assessed for the exclusive detection of (13)C spin pairs in sugar (D-[1,2-(13)C(2)]glucose) and inhibitor ([7-O(13)CO(13)CH(3)]forskolin) bound to the GalP protein. The solid state NMR methodology was not effective in creating double-quantum selection of ligand bound with membranes in the 'fluid' state (approx. 2 degrees C) but could be applied in a straightforward way to systems that were kept frozen. At -35 degrees C, double-quantum filtration detected unbound sugar that was incorporated into ice structure within the sample, and was not distinguished from protein-bound sugar. However, the method detected doubly labelled forskolin that is selectively bound only to the transport system under these conditions and provided very effective suppression of interference from natural abundance (13)C background. These results indicate that solid state NMR methods can be used to resolve selectively the interactions of more hydrophobic ligands in the binding sites of target proteins. 相似文献
72.
Rogalski SL Appleyard SM Pattillo A Terman GW Chavkin C 《The Journal of biological chemistry》2000,275(33):25082-25088
G protein-activated inwardly rectifying potassium channels (Kir3) are widely expressed throughout the brain, and regulation of their activity modifies neuronal excitability and synaptic transmission. In this study, we show that the neurotrophin brain-derived neurotrophic factor (BDNF), through activation of TrkB receptors, strongly inhibited the basal activity of Kir3. This inhibition was subunit dependent as functional homomeric channels of either Kir3.1 or Kir3.4 were significantly inhibited, whereas homomeric channels composed of Kir3.2 were insensitive. The general tyrosine kinase inhibitors genistein, G? 6976, and K252a but not the serine/threonine kinase inhibitor staurosporine blocked the BDNF-induced inhibition of the channel. BDNF was also found to directly stimulate channel phosphorylation because Kir3.1 immunoprecipitated from BDNF-stimulated cells showed enhanced labeling by anti-phosphotyrosine-specific antibodies. The BDNF effect required specific tyrosine residues in the amino terminus of Kir3.1 and Kir3.4 channels. Mutations of either Tyr-12, Tyr-67, or both in Kir3.1 or mutation of either Tyr-32, Tyr-53, or both of Kir3. 4 channels to phenylalanine significantly blocked the BDNF-induced inhibition. The insensitive Kir3.2 was made sensitive to BDNF by adding a tyrosine (D41Y) and a lysine (P32K) upstream to generate a phosphorylation site motif analogous to that present in Kir3.4. These results suggest that neurotrophin activation of TrkB receptors may physiologically control neuronal excitability by direct tyrosine phosphorylation of the Kir3.1 and Kir3.4 subunits of G protein-gated inwardly rectifying potassium channels. 相似文献
73.
74.
Spontaneous and evoked secretion of acetylcholinesterase from the hippocampus in vivo has been demonstrated by the use of push-pull cannulae. Local perfusion with 10−5M carbachol evoked an increase of 104% in acetylcholinesterase release with no accompanying change in butyrylcholinesterase or lactic dehydrogenase. Local or systemic atropine sulphate blocked the carbachol-evoked increase in acetylcholinesterase release, whilst gallamine had no effect. Local perfusion of γ-aminobutyric acid (10−4M) also blocked the carbachol-evoked release of acetylcholinesterase but had no effect on the spontaneous release.
It is concluded that a soluble form of acetylcholinesterase is secreted from the hippocampus in response to stimulation of muscarinic receptors; this secretion can be influenced by γ-aminobutyric acid, which is present in interneurones in the hippocampus. 相似文献
75.
76.
77.
In the last decade, treatment for castration-resistant prostate cancer has changed markedly, impacting symptom control and longevity for patients. However, a large proportion of cases progress despite androgen deprivation therapy and chemotherapy, while still being fit enough for several more lines of treatment. Overstimulation of the androgen receptor (AR) activity is the main driver of this cancer. Targeting biological functions of the AR or its co-regulators has proven very effective in this disease and led to the development of several highly effective drugs targeting the AR signalling axis. Drugs such as enzalutamide demonstrated that the improvement in anti-tumour efficacy is closely correlated with an affinity for the AR and its activity and have established the paradigm that AR remains activity in aggressive disease. However, as importantly, key insights into mechanisms of resistance are guiding the development of the next generation of AR-targeted drugs. This review outlines the historical development of these highly specific agents, their mechanism of action in the context of defective AR activity, and explores the potential for the upcoming next-generation AR inhibitors (ARI) for prostate cancer by targeting the alternative domains of AR, rather than by the conventional ligand-binding domain approach. There is huge potential in these approaches to develop new drugs with high clinical activity and further improve the outlook for patients. 相似文献
78.