全文获取类型
收费全文 | 135篇 |
免费 | 9篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 9篇 |
2020年 | 1篇 |
2019年 | 6篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 8篇 |
2014年 | 9篇 |
2013年 | 16篇 |
2012年 | 10篇 |
2011年 | 11篇 |
2010年 | 5篇 |
2009年 | 7篇 |
2008年 | 3篇 |
2007年 | 11篇 |
2006年 | 2篇 |
2005年 | 6篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1995年 | 3篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1989年 | 2篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1971年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有144条查询结果,搜索用时 31 毫秒
61.
A. Mesut Erzurumluoglu Muslim M. Alsaadi Santiago Rodriguez Tahani S. Alotaibi Philip A. I. Guthrie Sian Lewis Aasiya Ginwalla Tom R. Gaunt Khalid K. Alharbi Fahad M. Alsaif Basma M. Alsaadi Ian N. M. Day 《PloS one》2015,10(3)
Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder characterised by severe early onset periodontitis and palmoplantar hyperkeratosis. A previously reported missense mutation in the CTSC gene (NM_001814.4:c.899G>A:p.(G300D)) was identified in a homozygous state in two siblings diagnosed with PLS in a consanguineous family of Arabic ancestry. The variant was initially identified in a heterozygous state in a PLS unaffected sibling whose whole exome had been sequenced as part of a previous Primary ciliary dyskinesia study. Using this information, a proxy molecular diagnosis was made on the PLS affected siblings after consent was given to study this second disorder found to be segregating within the family. The prevalence of the mutation was then assayed in the local population using a representative sample of 256 unrelated individuals. The variant was absent in all subjects indicating that the variant is rare in Saudi Arabia. This family study illustrates how whole-exome sequencing can generate findings and inferences beyond its primary goal. 相似文献
62.
63.
The large number of variables involved in many biophysical models can conceal potentially simple dynamical mechanisms governing
the properties of its solutions and the transitions between them as parameters are varied. To address this issue, we extend
a novel model reduction method, based on “scales of dominance,” to multi-compartment models. We use this method to systematically
reduce the dimension of a two-compartment conductance-based model of a crustacean pyloric dilator (PD) neuron that exhibits
distinct modes of oscillation—tonic spiking, intermediate bursting and strong bursting. We divide trajectories into intervals
dominated by a smaller number of variables, resulting in a locally reduced hybrid model whose dimension varies between two
and six in different temporal regimes. The reduced model exhibits the same modes of oscillation as the 16 dimensional model
over a comparable parameter range, and requires fewer ad hoc simplifications than a more traditional reduction to a single,
globally valid model. The hybrid model highlights low-dimensional organizing structure in the dynamics of the PD neuron, and
the dependence of its oscillations on parameters such as the maximal conductances of calcium currents. Our technique could
be used to build hybrid low-dimensional models from any large multi-compartment conductance-based model in order to analyze
the interactions between different modes of activity. 相似文献
64.
Nicolas Marsollier Nadim Kassis Karima Mezghenna Maud Soty Xavier Fioramonti Amélie Lacombe Aurélie Joly Bruno Pillot Carine Zitoun José Vilar Gilles Mithieux René Gross Anne-Dominique Lajoix Vanessa Routh Christophe Magnan Céline Cruciani-Guglielmacci 《PloS one》2009,4(8)
Background
Deregulation of hypothalamic fatty acid sensing lead to hepatic insulin-resistance which may partly contribute to further impairment of glucose homeostasis.Methodology
We investigated here whether hypothalamic nitric oxide (NO) could mediate deleterious peripheral effect of central lipid overload. Thus we infused rats for 24 hours into carotid artery towards brain, either with heparinized triglyceride emulsion (Intralipid, IL) or heparinized saline (control rats).Principal Findings
Lipids infusion led to hepatic insulin-resistance partly related to a decreased parasympathetic activity in the liver assessed by an increased acetylcholinesterase activity. Hypothalamic nitric oxide synthases (NOS) activities were significantly increased in IL rats, as the catalytically active neuronal NOS (nNOS) dimers compared to controls. This was related to a decrease in expression of protein inhibitor of nNOS (PIN). Effect of IL infusion on deregulated hepatic insulin-sensitivity was reversed by carotid injection of non selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) and also by a selective inhibitor of the nNOS isoform, 7-Nitro-Indazole (7-Ni). In addition, NO donor injection (L-arginine and SNP) within carotid in control rats mimicked lipid effects onto impaired hepatic insulin sensitivity. In parallel we showed that cultured VMH neurons produce NO in response to fatty acid (oleic acid).Conclusions/Significance
We conclude that cerebral fatty acid overload induces an enhancement of nNOS activity within hypothalamus which is, at least in part, responsible fatty acid increased hepatic glucose production. 相似文献65.
Maryline Paris Catherine Bernard-Kargar José Vilar Nadim Kassis Alain Ktorza 《Experimental diabetes research》2004,5(4):257-263
We investigated the possible interplay between insulin
and glucose signaling pathways in rat pancreatic β-cell
with a special focus on the role of glucose in IRS signaling
in vivo. Three groups of rats were constituted by combining
simultaneous infusion during 48 h either of glucose
and/or insulin, or glucose+diazoxide: Hyperglycemic-
Hyperinsulinemic (HGHI), euglycemic-Hyperinsulinemic
(eGHI), Hyperglycemic-euinsulinemic (HGeI). Control rats
were infused with 0,9% NaCl. In HGHI and HGeI rats
plasma glucose levels were maintained at 20-22 mmol/l. In
eGHI rats, plasma glucose was not different from that of
controls, whereas plasma insulin was much higher than
in controls. In HGHI rats, IRS-2 mRNA expression, total
protein and phosphorylated protein amounts were increased
compared to controls. In HGeI rats, only IRS-2
mRNA expression was increased. No change was observed
in eGHI rats whatever the parameter considered. In all
groups, mRNA concentration of IRS-1 was similar to that
of controls. The quantity of total and phosphorylated IRS-
1 protein was dramatically increased in HGHI rats and
to a lesser extent in eGHI rats. Neither mRNA nor IRS-1
protein expression were modified in HGeI rats. The data
suggest that glucose and insulin play at once a specific
and a complementary role in islet IRSs signaling. Especially,
glucose stimulates IRS-2 mRNA expression whatever
the insulin status and independently of the secretory
process. The differential regulation of IRS-1 and
IRS-2 expressions is in agreement with their supposed different involvement in the control of β-cell growth and
function. 相似文献
66.
The transient potassium A-current is present in most neurons and plays an important role in determining the timing of action potentials. We examine the role of the A-current in the activity phase of a follower neuron in a rhythmic feed-forward inhibitory network with a reduced three-variable model and conduct experiments to verify the usefulness of our model. Using geometric analysis of dynamical systems, we explore the factors that determine the onset of activity in a follower neuron following release from inhibition. We first analyze the behavior of the follower neuron in a single cycle and find that the phase plane structure of the model can be used to predict the potential behaviors of the follower neuron following release from inhibition. We show that, depending on the relative scales of the inactivation time constant of the A-current and the time constant of the recovery variable, the follower neuron may or may not reach its active state following inhibition. Our simple model is used to derive a recursive set of equations to predict the contribution of the A-current parameters in determining the activity phase of a follower neuron as a function of the duration and frequency of the inhibitory input it receives. These equations can be used to demonstrate the dependence of activity phase on the period and duty cycle of the periodic inhibition, as seen by comparing the predictions of the model with the activity of the pyloric constrictor (PY) neurons in the crustacean pyloric network. 相似文献
67.
68.
Proprotein convertases (PCs) have been proposed to play a role in tumor necrosis factor-alpha converting enzyme (TACE) processing/activation. Using the furin-deficient LoVo cells, as well as the furin-proficient synoviocytes and HT1080 cells expressing the furin inhibitor alpha(1)-PDX, we demonstrate that furin activity alone is not sufficient for effective maturation and activation of the TACE enzyme. Data from in vitro and in vivo cleavage assays indicate that PACE-4, PC5/PC6, PC1 and PC2 can directly cleave the TACE protein and/or peptide. PC inhibition in macrophages reduced the release of soluble TNF-alpha from transmembrane pro-TNF-alpha. We therefore conclude that furin, in addition to other candidate PCs, is involved in TACE maturation and activation. 相似文献
69.
Translation of the stationary phase sigma factor RpoS is stimulated by at least two small RNAs, DsrA and RprA. DsrA disrupts an inhibitory secondary structure in the rpoS leader mRNA by pairing with the upstream RNA. Mutations in rprA and compensating mutations in the rpoS leader demonstrate that RprA interacts with the same region of the RpoS leader as DsrA. This is the first example of two different small RNAs regulating a common target. Regulation of these RNAs differs. DsrA synthesis is increased at low temperature. We find that RprA synthesis is regulated by the RcsC/RcsB phosphorelay system, previously found to regulate capsule synthesis and promoters of ftsZ and osmC. An rcsB null mutation abolishes the basal level, whereas mutations in rcsC that activate capsule synthesis also activate expression of the rprA promoter. An essential site with similarity to other RcsB-regulated promoters was defined in the rprA promoter. Activation of the RcsC/RcsB system leads to increased RpoS synthesis, in an RprA-dependent fashion. This work suggests a new signal for RpoS translation and extends the global regulation effected by the RcsC/RcsB system to coregulation of RpoS with capsule and FtsZ. 相似文献
70.
Development of two major resources for pea genomics: the GenoPea 13.2K SNP Array and a high‐density,high‐resolution consensus genetic map 下载免费PDF全文
Nadim Tayeh Christelle Aluome Matthieu Falque Françoise Jacquin Anthony Klein Aurélie Chauveau Aurélie Bérard Hervé Houtin Céline Rond Jonathan Kreplak Karen Boucherot Chantal Martin Alain Baranger Marie‐Laure Pilet‐Nayel Thomas D. Warkentin Dominique Brunel Pascal Marget Marie‐Christine Le Paslier Grégoire Aubert Judith Burstin 《The Plant journal : for cell and molecular biology》2015,84(6):1257-1273