全文获取类型
收费全文 | 247篇 |
免费 | 19篇 |
出版年
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 1篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 13篇 |
2013年 | 5篇 |
2012年 | 17篇 |
2011年 | 14篇 |
2010年 | 12篇 |
2009年 | 9篇 |
2008年 | 9篇 |
2007年 | 14篇 |
2006年 | 6篇 |
2005年 | 13篇 |
2004年 | 12篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 11篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 11篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1948年 | 1篇 |
1934年 | 1篇 |
1901年 | 1篇 |
排序方式: 共有266条查询结果,搜索用时 250 毫秒
1.
Lithium Selectively Inhibits Muscarinic Receptor-Stimulated Inositol Tetrakisphosphate Accumulation in Mouse Cerebral Cortex Slices 总被引:13,自引:6,他引:7
The in vitro effects of Li on agonist- and depolarization-stimulated accumulation of inositol phosphates were determined in mouse cerebral cortex slices. Of the agents examined, only the cholinergic agonist carbachol produced a significant accumulation of inositol tetrakisphosphate (InsP4) in the absence of Li. Lithium at 5 mM enhanced the accumulation of inositol monophosphate (InsP1) and inositol bisphosphate (InsP2) due to all the stimuli used and potentiated inositol trisphosphate (InsP3) accumulation due to histamine and noradrenaline, although at lower Li concentrations, carbachol-stimulated InsP3 accumulation was reduced. Li also enhanced InsP4 accumulation in the presence of noradrenaline, histamine, and elevated KCl level but, in marked contrast, reduced carbachol-stimulated InsP4 accumulation with an IC50 of 100 microM. There was a significant time delay between the initiation of carbachol stimulation and the beginning of the InsP4 inhibition due to Li. The phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate did not mimic the effects of Li. The results suggest that muscarinic receptor-mediated InsP4 production might be one of the targets for the therapeutic action of Li. 相似文献
2.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4
下载免费PDF全文
![点击此处可从《The Journal of general physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
3.
Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of phylogenetic signal 总被引:10,自引:9,他引:1
We have developed a new approach to the measurement of phylogenetic signal
in character state matrices called relative apparent synapomorphy analysis
(RASA). RASA provides a deterministic, statistical measure of natural
cladistic hierarchy (phylogenetic signal) in character state matrices. The
method works by determining whether a measure of the rate of increase of
cladistic similarity among pairs of taxa as a function of phenetic
similarity is greater than a null equiprobable rate of increase. Our
investigation of the utility and limitations of RASA using simulated and
bacteriophage T7 data sets indicates that the method has numerous
advantages over existing measures of signal. A first advantage is
computational efficiency. A second advantage is that RASA employs known
methods of statistical inference, providing measurable sensitivity and
power. The performance of RASA is examined under various conditions of
branching evolution as the number of characters, character states per
character, and mutations per branch length are varied. RASA appears to
provide an unbiased and reliable measure of phylogenetic signal, and the
general approach promises to be useful in the development of new techniques
that should increase the rigor and reliability of phylogenetic estimates.
相似文献
4.
5.
Variation in heat-shock proteins among species of desert fishes (Poeciliidae, Poeciliopsis) 总被引:4,自引:0,他引:4
Analysis of the heat-shock proteins (hsps) of six closely related species
of Poeciliopsis demonstrated the existence of biochemical diversity in the
hsp100, hsp70, hsp60, and hsp30 protein families among species. Each
species expressed five to seven hsp70-related isoforms. Constitutive 70-kD
isoforms were identical among species, but four different patterns of
heat-inducible isoforms were seen in these six species. Members of the
hsp70 family of molecular chaperones are included among the most highly
conserved proteins known, and the possibility of variation in hsp70 among
closely related species has rarely been addressed. The hsp30 family is
known to be less conserved than the hsp70 family, and, as expected, the
Poeciliopsis hsp30 patterns showed more variation. Most of the hsp30
isoforms characteristic of a particular species were unique to that
species. Hsp100 and hsp60 were identical in five of the species, but
alternate isoforms were found in P. monacha. The small size and limited
geographical distribution of the P. monacha population have probably
contributed to the uniqueness of the monacha pattern. Two of the species
were shown to acquire thermotolerance, the ability to withstand normally
lethal temperatures when subjected to a gradual temperature increase.
Rapid-heating protocols commonly used to establish critical thermal maxima
of organisms do not include this inducible component of thermoresistance
and therefore do not adequately assess an organism's capacity to withstand
thermal stress.
相似文献
6.
Variation in heat shock proteins within tropical and desert species of poeciliid fishes 总被引:8,自引:0,他引:8
Norris CE; diIorio PJ; Schultz RJ; Hightower LE 《Molecular biology and evolution》1995,12(6):1048-1062
The 70-kilodalton heat shock protein (hsp70) family of molecular
chaperones, which contains both stress-inducible and normally abundant
constitutive members, is highly conserved across distantly related taxa.
Analysis of this protein family in individuals from an outbred population
of tropical topminnows, Poeciliopsis gracilis, showed that while
constitutive hsp70 family members showed no variation in protein isoforms,
inducibly synthesized hsp70 was polymorphic. Several species of
Poeciliopsis adapted to desert environments exhibited lower levels of
inducible hsp70 polymorphism than the tropical species, but constitutive
forms were identical to those in P. gracilis, as they were in the
confamilial species Gambusia affinis. These differences suggest that
inducible and constitutive members of this family are under different
evolutionary constraints and may indicate differences in their function
within the cell. Also, northern desert species of Poeciliopsis synthesize a
subset of the inducible hsp70 isoforms seen in tropical species. This
distribution supports the theory that ancestral tropical fish migrated
northward and colonized desert streams; the subsequent decrease in
variation of inducible hsp70 may have been due to genetic drift or a
consequence of adaptation to the desert environment. Higher levels of
variability were found when the 30- kilodalton heat shock protein (hsp30)
family was analyzed within different strains of two desert species of
Poeciliopsis and also in wild-caught individuals of Gambusia affinis. In
both cases the distribution of hsp30 isoform diversity was similar to that
seen previously with allozyme polymorphisms.
相似文献
7.
8.
R T Mason J P Coghlan D A Denton D W Fei B A Scoggins J A Whitworth 《Prostaglandins》1984,27(4):527-534
The haemodynamic and renin responses to prostacyclin (PGI2) infusion were examined in sheep during sodium depletion and dietary sodium restriction. The haemodynamic effects of PGI2 infusion in sodium depleted and sodium restricted sheep were similar to those obtained in the sodium replete animal. The renin proportionate response to PGI2 was not altered by sodium restriction but blunted by sodium depletion, compatible with the hypothesis that endogenous PGI2 is high in Na depletion. 相似文献
9.
Whitworth J 《Parasitology today (Personal ed.)》1992,8(4):138-140
Ivermectin chemotherapy is proving to be a major advance in the management of onchocerciasis. In this article, James Whitworth reviews the work done on onchocerciasis and ivermectin in Sierra Leone and examines the evidence that mass treatment might control the clinical features of the disease and its transmission in West Africa. Ivermectin is safe and effectively reduces microfilarial (mf) loads, with major improvement in some ocular manifestations o f disease. This alone makes mass distribution to communities at risk of blindness worthwhile, even though the impact on other clinical features is less clear cut. Repeated doses have a cumulative effect on adult worms, which may cause more reduction in transmission than hitherto thought likely. 相似文献
10.
Joanne L Usher Alvaro SanchezMartinez Ana TerrienteFelix PoLin Chen Juliette J Lee ChunHong Chen Alexander J Whitworth 《EMBO reports》2022,23(12)
Parkinson''s disease‐related proteins, PINK1 and Parkin, act in a common pathway to maintain mitochondrial quality control. While the PINK1‐Parkin pathway can promote autophagic mitochondrial turnover (mitophagy) following mitochondrial toxification in cell culture, alternative quality control pathways are suggested. To analyse the mechanisms by which the PINK1–Parkin pathway operates in vivo, we developed methods to detect Ser65‐phosphorylated ubiquitin (pS65‐Ub) in Drosophila. Exposure to the oxidant paraquat led to robust, Pink1‐dependent pS65‐Ub production, while pS65‐Ub accumulates in unstimulated parkin‐null flies, consistent with blocked degradation. Additionally, we show that pS65‐Ub specifically accumulates on disrupted mitochondria in vivo. Depletion of the core autophagy proteins Atg1, Atg5 and Atg8a did not cause pS65‐Ub accumulation to the same extent as loss of parkin, and overexpression of parkin promoted turnover of both basal and paraquat‐induced pS65‐Ub in an Atg5‐null background. Thus, we have established that pS65‐Ub immunodetection can be used to analyse Pink1‐Parkin function in vivo as an alternative to reporter constructs. Moreover, our findings suggest that the Pink1‐Parkin pathway can promote mitochondrial turnover independently of canonical autophagy in vivo. 相似文献