全文获取类型
收费全文 | 118篇 |
免费 | 11篇 |
出版年
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2015年 | 7篇 |
2014年 | 3篇 |
2013年 | 4篇 |
2012年 | 5篇 |
2011年 | 7篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 6篇 |
2006年 | 7篇 |
2005年 | 7篇 |
2004年 | 7篇 |
2003年 | 1篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 11篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1977年 | 1篇 |
排序方式: 共有129条查询结果,搜索用时 31 毫秒
1.
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
2.
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
3.
4.
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
5.
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
6.
7.
8.
Sascha Venturelli Alexander Berger Alexander B?cker Christian Busch Timo Weiland Seema Noor Christian Leischner Sabine Schleicher Mascha Mayer Thomas S. Weiss Stephan C. Bischoff Ulrich M. Lauer Michael Bitzer 《PloS one》2013,8(8)
The polyphenolic alcohol resveratrol has demonstrated promising activities for the prevention and treatment of cancer. Different modes of action have been described for resveratrol including the activation of sirtuins, which represent the class III histone deacetylases (HDACs). However, little is known about the activity of resveratrol on the classical HDACs of class I, II and IV, although these classes are involved in cancer development or progression and inhibitors of HDACs (HDACi) are currently under investigation as promising novel anticancer drugs. We could show by in silico docking studies that resveratrol has the chemical structure to inhibit the activity of different human HDAC enzymes. In vitro analyses of overall HDAC inhibition and a detailed HDAC profiling showed that resveratrol inhibited all eleven human HDACs of class I, II and IV in a dose-dependent manner. Transferring this molecular mechanism into cancer therapy strategies, resveratrol treatment was analyzed on solid tumor cell lines. Despite the fact that hepatocellular carcinoma (HCC) is known to be particularly resistant against conventional chemotherapeutics, treatment of HCC with established HDACi already has shown promising results. Testing of resveratrol on hepatoma cell lines HepG2, Hep3B and HuH7 revealed a dose-dependent antiproliferative effect on all cell lines. Interestingly, only for HepG2 cells a specific inhibition of HDACs and in turn a histone hyperacetylation caused by resveratrol was detected. Additional testing of human blood samples demonstrated a HDACi activity by resveratrol ex vivo. Concluding toxicity studies showed that primary human hepatocytes tolerated resveratrol, whereas in vivo chicken embryotoxicity assays demonstrated severe toxicity at high concentrations. Taken together, this novel pan-HDACi activity opens up a new perspective of resveratrol for cancer therapy alone or in combination with other chemotherapeutics. Moreover, resveratrol may serve as a lead structure for chemical optimization of bioavailability, pharmacology or HDAC inhibition. 相似文献
9.
Our research explores the feasibility of using communication theory, error control (EC) coding theory specifically, for quantitatively modeling the protein translation initiation mechanism. The messenger RNA (mRNA) of Escherichia coli K-12 is modeled as a noisy (errored), encoded signal and the ribosome as a minimum Hamming distance decoder, where the 16S ribosomal RNA (rRNA) serves as a template for generating a set of valid codewords (the codebook). We tested the E. coli based coding models on 5' untranslated leader sequences of prokaryotic organisms of varying taxonomical relation to E. coli including: Salmonella typhimurium LT2, Bacillus subtilis, and Staphylococcus aureus Mu50. The model identified regions on the 5' untranslated leader where the minimum Hamming distance values of translated mRNA sub-sequences and non-translated genomic sequences differ the most. These regions correspond to the Shine-Dalgarno domain and the non-random domain. Applying the EC coding-based models to B. subtilis, and S. aureus Mu50 yielded results similar to those for E. coli K-12. Contrary to our expectations, the behavior of S. typhimurium LT2, the more taxonomically related to E. coli, resembled that of the non-translated sequence group. 相似文献
10.