全文获取类型
收费全文 | 294篇 |
免费 | 22篇 |
国内免费 | 16篇 |
出版年
2023年 | 33篇 |
2022年 | 13篇 |
2021年 | 34篇 |
2020年 | 15篇 |
2019年 | 21篇 |
2018年 | 7篇 |
2017年 | 9篇 |
2016年 | 10篇 |
2015年 | 26篇 |
2014年 | 14篇 |
2013年 | 11篇 |
2012年 | 7篇 |
2011年 | 16篇 |
2010年 | 4篇 |
2009年 | 7篇 |
2008年 | 3篇 |
2007年 | 7篇 |
2006年 | 14篇 |
2005年 | 10篇 |
2004年 | 4篇 |
2003年 | 7篇 |
2002年 | 8篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有332条查询结果,搜索用时 203 毫秒
51.
High-conductance calcium-activated potassium channels; Structure,pharmacology, and function 总被引:19,自引:0,他引:19
Gregory J. Kaczorowski Hans -Günther Knaus Reid J. Leonard Owen B. McManus Maria L. Garcia 《Journal of bioenergetics and biomembranes》1996,28(3):255-267
High-conductance calcium-activated potassium (maxi-K) channels comprise a specialized family of K+ channels. They are unique in their dual requirement for depolarization and Ca2+ binding for transition to the open, or conducting, state. Ion conduction through maxi-K channels is blocked by a family of venom-derived peptides, such as charybdotoxin and iberiotoxin. These peptides have been used to study function and structure of maxi-K channels, to identify novel channel modulators, and to follow the purification of functional maxi-K channels from smooth muscle. The channel consists of two dissimilar subunits, and . The subunit is a member of theslo Ca2+-activated K+ channel gene family and forms the ion conduction pore. The subunit is a structurally unique, membrane-spanning protein that contributes to channel gating and pharmacology. Potent, selective maxi-K channel effectors (both agonists and blockers) of low molecular weight have been identified from natural product sources. These agents, together with peptidyl inhibitors and site-directed antibodies raised against and subunit sequences, can be used to anatomically map maxi-K channel expression, and to study the physiologic role of maxi-K channels in various tissues. One goal of such investigations is to determine whether maxi-K channels represent novel therapeutic targets. 相似文献
52.
53.
Neuropeptide Y modulates the action of vasodilator agents in guinea-pig epicardial coronary arteries
S rgio Gulbenkian Lars Edvinsson Ole Saetrum Opgaard Angela Valen a John Wharton Julia M. Polak 《Regulatory peptides》1992,40(3):351-362
Recently, we have demonstrated that guinea-pig epicardial coronary arteries are supplied by numerous nerve fibres containing neuropeptide Y (NPY) immunoreactivity. However, examination of vasomotor responses revealed that NPY did not elicit a contractile response in these arteries. In contrast, acetylcholine (ACh), calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP) all relaxed precontracted arteries. In the present study, we have used histochemical, immunohistochemical and in vitro pharmacological techniques, in order to further investigate the possible role of NPY in guinea-pig epicardial coronary arteries. A double-immunofluorescence staining technique revealed that CGRP and substance P were co-localized in nerve fibres distinct from those displaying NPY immunoreactivity. Furthermore, using a method combining immunofluorescence and histochemical techniques, we observed that putative cholinergic nerve fibres (identified by their acetylcholinesterase content) and NPY-immunoreactive nerve fibres are two different nerve populations. An in vitro pharmacological method demonstrated that NPY markedly inhibited the relaxant responses mediated by ACh, VIP, substance P and isoprenaline but had no effect on CGRP. These results suggest that NPY-containing nerves associated with guinea-pig epicardial coronary arteries may be predominantly involved in modulating the action of vasodilator agents. 相似文献
54.
Antitumor evaluation of marine algae in Argentina 总被引:3,自引:3,他引:0
55.
紫草的化学成分及其药理活性研究概况 总被引:31,自引:0,他引:31
本文对国内外有关药用植物紫草的化学成分、它们的提取分离及生物合成以及药理活性等方面的研究进行了综述,为研究和开发利用紫草提供依据。 相似文献
56.
57.
This study was implemented to test the Episkin model of reconstructed epidermis in the evaluation of the efficacy of cosmetic or dermopharmaceutical products on cutaneous energy metabolism. The energy metabolism is evaluated by measuring the concentration of intracellular ATP by a method using an ultrasensitive bioluminescent reaction. The work presented compares results obtained in reconstructed epithelium and monolayer primary cultures of human keratinocytes.After application of a hydrosoluble product, the increase in intracellular ATP is identical in a monolayer culture of keratinocytes (+239±18% versus control) and in Episkin (+248±21% versus control). An emulsion was also tested on the two models. It is only possible to test the emulsion at a dilution of under 0.05% on a keratinocyte culture, and this means that the real efficacy of the product is underestimated (+145±18% versus control). The three-dimensional model enables the application of the undiluted emulsion, and the results show an increase in intracellular ATP of +420±80% versus control: products in final formulation can be tested in normal conditions of use.Abbreviations BPE
bovine pituitary extract
- DMEM
Dulbecco's modified Eagle's medium
- EDTA
ethylene diamine tetraacetic acid
- EGF
epidermal growth factor
- K-SFM
keratinocytes serum free medium
- MTT
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
- O/W
oil in water
- PBS
phosphate-buffered saline 相似文献
58.
59.
Das A Pushparaj C Bahí N Sorolla A Herreros J Pamplona R Vilella R Matias-Guiu X Martí RM Cantí C 《Pigment cell & melanoma research》2012,25(2):200-212
The expression of voltage-gated calcium channels (VGCCs) has not been reported previously in melanoma cells in spite of increasing evidence of a role of VGCCs in tumorigenesis and tumour progression. To address this issue we have performed an extensive RT-PCR analysis of VGCC expression in human melanocytes and a range of melanoma cell lines and biopsies. In addition, we have tested the functional expression of these channels using Ca(2+) imaging techniques and examined their relevance for the viability and proliferation of the melanoma cells. Our results show that control melanocytes and melanoma cells express channel isoforms belonging to the Ca(v) 1 and Ca(v) 2 gene families. Importantly, the expression of low voltage-activated Ca(v) 3 (T-type) channels is restricted to melanoma. We have confirmed the function of T-type channels as mediators of constitutive Ca(2+) influx in melanoma cells. Finally, pharmacological and gene silencing approaches demonstrate a role for T-type channels in melanoma viability and proliferation. These results encourage the analysis of T-type VGCCs as targets for therapeutic intervention in melanoma tumorigenesis and/or tumour progression. 相似文献
60.
In our recent publication, we describe the local anesthetic (LA) inhibition of the prokaryotic voltage gated sodium channel NaChBac. Despite the numerous functional and putative structural differences with the mammalian sodium channels, the data show that LA compounds effectively and reversibly inhibit NaChBac channels in a concentration range similar to resting blockade on eukaryotic Navs. In addition to current reduction, LA application accelerated channel inactivation kinetics of NaChBac which could be accounted for in a simple state-model whereby local anesthetics increase the probability of entering the inactivated state. We have further explored what state (or states) local anesthetic blockade of NaChBac could pertain to eukaryotic sodium channels, and what molecular similarities exist between these disparate channel families. Here we show that the rate of recovery from inactivation remains unaffected in the presence of local anesthetics. Further, we show that two sites that support use-dependent inhibition in eukaryotic channels, do not affect block to the same extent when mutated in NaChBac channels. The data indicate that the molecular determinants and the inherent mechanisms for LA block are likely to be divergent between bacterial and eukaryotic Navs, but future experiments will help define possible similarities. 相似文献