全文获取类型
收费全文 | 526篇 |
免费 | 51篇 |
出版年
2024年 | 2篇 |
2023年 | 6篇 |
2022年 | 6篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 12篇 |
2017年 | 6篇 |
2016年 | 14篇 |
2015年 | 34篇 |
2014年 | 30篇 |
2013年 | 37篇 |
2012年 | 38篇 |
2011年 | 49篇 |
2010年 | 29篇 |
2009年 | 37篇 |
2008年 | 35篇 |
2007年 | 30篇 |
2006年 | 24篇 |
2005年 | 30篇 |
2004年 | 21篇 |
2003年 | 15篇 |
2002年 | 26篇 |
2001年 | 5篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1991年 | 2篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 8篇 |
1970年 | 4篇 |
1968年 | 2篇 |
1965年 | 2篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1959年 | 1篇 |
1956年 | 2篇 |
1953年 | 1篇 |
1952年 | 1篇 |
排序方式: 共有577条查询结果,搜索用时 15 毫秒
111.
Hoyt SB London C Wyvratt MJ Fisher MH Cashen DE Felix JP Garcia ML Li X Lyons KA Euan MacIntyre D Martin WJ Priest BT Smith MM Warren VA Williams BS Kaczorowski GJ Parsons WH 《Bioorganic & medicinal chemistry letters》2008,18(6):1963-1966
A series of 3-amino-1,5-benzodiazepinones were synthesized and evaluated as potential sodium channel blockers in a functional, membrane potential-based assay. One member of this series displayed subnanomolar, state-dependent sodium channel block, and was orally efficacious in a mouse model of epilepsy. 相似文献
112.
Liu XW Ma J Colson AO Doersen DC Ebetino FH 《Bioorganic & medicinal chemistry letters》2008,18(3):1223-1228
A series of novel peptidomimetic analogs was prepared containing cyclohexyl, phenyl, or heterocyclic groups to ostensibly orient the guanidine or mimic of an arginine in a putative melanocortin receptor ligand pharmacophore. Some binding affinity at the melanocortin receptors MC(3) and MC(4) was noted. In silico docking also indicated that the relative positions of the hydrogen-bonding sites and hydrophobic regions of the compounds are reasonably well matched to the receptor-binding site. This may present a lead entry into a selective series of MC(4)R agonists. 相似文献
113.
Matthieu Gilson Anthony N. Burkitt David B. Grayden Doreen A. Thomas J. Leo van Hemmen 《Biological cybernetics》2009,101(2):103-114
Spike-timing-dependent plasticity (STDP) is believed to structure neuronal networks by slowly changing the strengths (or weights)
of the synaptic connections between neurons depending upon their spiking activity, which in turn modifies the neuronal firing
dynamics. In this paper, we investigate the change in synaptic weights induced by STDP in a recurrently connected network
in which the input weights are plastic but the recurrent weights are fixed. The inputs are divided into two pools with identical
constant firing rates and equal within-pool spike-time correlations, but with no between-pool correlations. Our analysis uses
the Poisson neuron model in order to predict the evolution of the input synaptic weights and focuses on the asymptotic weight
distribution that emerges due to STDP. The learning dynamics induces a symmetry breaking for the individual neurons, namely
for sufficiently strong within-pool spike-time correlation each neuron specializes to one of the input pools. We show that
the presence of fixed excitatory recurrent connections between neurons induces a group symmetry-breaking effect, in which
neurons tend to specialize to the same input pool. Consequently STDP generates a functional structure on the input connections
of the network. 相似文献
114.
Matthieu Gilson Anthony N. Burkitt David B. Grayden Doreen A. Thomas J. Leo van Hemmen 《Biological cybernetics》2009,101(2):81-102
Spike-timing-dependent plasticity (STDP) determines the evolution of the synaptic weights according to their pre- and post-synaptic
activity, which in turn changes the neuronal activity. In this paper, we extend previous studies of input selectivity induced
by (STDP) for single neurons to the biologically interesting case of a neuronal network with fixed recurrent connections and
plastic connections from external pools of input neurons. We use a theoretical framework based on the Poisson neuron model
to analytically describe the network dynamics (firing rates and spike-time correlations) and thus the evolution of the synaptic
weights. This framework incorporates the time course of the post-synaptic potentials and synaptic delays. Our analysis focuses
on the asymptotic states of a network stimulated by two homogeneous pools of “steady” inputs, namely Poisson spike trains
which have fixed firing rates and spike-time correlations. The (STDP) model extends rate-based learning in that it can implement,
at the same time, both a stabilization of the individual neuron firing rates and a slower weight specialization depending
on the input spike-time correlations. When one input pathway has stronger within-pool correlations, the resulting synaptic
dynamics induced by (STDP) are shown to be similar to those arising in the case of a purely feed-forward network: the weights
from the more correlated inputs are potentiated at the expense of the remaining input connections. 相似文献
115.
Caryll Waugh Linda Sinclair David Finlay Jose R. Bayascas Doreen Cantrell 《Molecular and cellular biology》2009,29(21):5952-5962
116.
Friedrich Schöne Matthias Leiterer Peter Lebzien Doreen Bemmann Markus Spolders Gerhard Flachowsky 《Journal of trace elements in medicine and biology》2009,23(2):84-92
Most feed is poor in iodine and iodine supplementation of cow's diets must guarantee milk iodine concentrations for humans that contribute to prevention of the deficiency and minimize the risk of exceeding an upper limit of iodine intake. Five Holstein cows were fed four iodine doses (via Ca(ΙO3)2·6H2O). In four sequential 14-d periods, doses of 0.2 (basal diet), 1.3, 5.1, and 10.1 mg iodine kg?1 diet dry matter (DM) were administered. Samples of milk were collected during each period; blood was also sampled from each cow for each iodine dosage. In an 18-d depletion period, a non-supplemented diet was provided. Iodine was determined by inductively coupled plasma-mass spectrometry. The iodine content of milk and serum reflected the iodine dosages in feed significantly. The levels for the four doses tested in milk were 101±32, 343±109, 1215±222, and 2762±852 μg iodine kg?1. The total amount of iodine in milk per day was 30–40% of ingested supplemental iodine. Omitting additional iodine resulted in a short-term reduction of serum and milk iodine following an exponential decay function. The iodine supplementation of 0.5–1.5 mg kg?1 diet DM represents the requirement of the cow, resulting in 100–300 μg iodine L?1 milk, which optimally contributes to human supply. The maximum dietary levels of former and present EU legislations (10 and 5 mg iodine kg?1 cow feed) increase the risk of iodine excess in humans. 相似文献
117.
Doreen Siegel Maximilian Schuff Franz Oswald Ying Cao Walter Knöchel 《Mechanisms of development》2009,126(11-12):974-989
The maintenance of pluripotency in mammalian embryonic stem cells depends upon the expression of regulatory genes like Oct3/4 and Sox2. While homologues of these genes are also characterized in non-mammalian vertebrates, like birds, amphibians and fish, existence and function of developmental pluripotency associated genes (Dppa) in lower vertebrates have not yet been reported. Here we describe a Dppa2/4-like gene, XDppa2/4, in Xenopus. The protein contains a SAP domain and a conserved C-terminal region. Overexpression of XDppa2/4, murine Dppa2 or Dppa4 produces similar phenotypes (defects in blastopore closure), while injection of XDppa2/4 morpholino generates a loss of blastopore closure and neural fold formation. Embryos die up to tailbud stage. mDppa2 (but not mDppa4) rescues blastopore closure and neurulation defects caused by XDppaMO, but does not prevent subsequent death of embryos. Although XDppa2/4 exhibits a Dppa-like expression pattern and is indispensable for embryogenesis, analyses of various marker genes make its role as a pluripotency factor rather unlikely. Both the gain and loss of function effects until the end of neurulation are caused by the conserved C-terminal region but not by the SAP domain. The SAP domain is required for association of XDppa2/4 to chromatin and for embryonic survival at later stages of development suggesting epigenetic programming events. 相似文献
118.
119.
Doreen Matthies Laura Preiss Adriana L. Klyszejko Gregory M. Cook Thomas Meier 《Journal of molecular biology》2009,388(3):611-4730
We have structurally characterized the c-ring from the thermoalkaliphilic Bacillus sp. strain TA2.A1 F1Fo-ATP synthase. Atomic force microscopy imaging and cryo-electron microscopy analyses confirm previous mass spectrometric data indicating that this c-ring contains 13 c-subunits. The cryo-electron microscopy map obtained from two-dimensional crystals shows less closely packed helices in the inner ring compared to those of Na+-binding c11 rings. The inner ring of α-helices in c11 rings harbors a conserved GxGxGxGxG motif, with glycines located at the interface between c-subunits, which is responsible for the close packing of these helices. This glycine motif is altered in the c13 ring of Bacillus sp. strain TA2.A1 to AxGxSxGxS, leading to a change in c-c subunit contacts and thereby enlarging the c-ring diameter to host a greater number of c-subunits. An altered glycine motif is a typical feature of c-subunit sequences in alkaliphilic Bacillus species. We propose that enlarged c-rings in proton-dependent F-ATP synthases may represent an adaptation to facilitate ATP synthesis at low overall proton-motive force, as occurs in bacteria that grow at alkaline pH. 相似文献
120.
Ubiquitination occurs at synapses, yet its role remains unclear. Previous studies demonstrated that the RPM-1 ubiquitin ligase organizes presynaptic boutons at neuromuscular junctions in C. elegans motorneurons. Here we find that RPM-1 has a novel postsynaptic role in interneurons, where it regulates the trafficking of the AMPA-type glutamate receptor GLR-1 from synapses into endosomes. Mutations in rpm-1 cause the aberrant accumulation of GLR-1 in neurites. Moreover, rpm-1 mutations enhance the endosomal accumulation of GLR-1 observed in mutants for lin-10, a Mint2 ortholog that promotes GLR-1 recycling from Syntaxin-13 containing endosomes. As in motorneurons, RPM-1 negatively regulates the pmk-3/p38 MAPK pathway in interneurons by repressing the protein levels of the MAPKKK DLK-1. This regulation of PMK-3 signaling is critical for RPM-1 function with respect to GLR-1 trafficking, as pmk-3 mutations suppress both lin-10 and rpm-1 mutations. Positive or negative changes in endocytosis mimic the effects of rpm-1 or pmk-3 mutations, respectively, on GLR-1 trafficking. Specifically, RAB-5(GDP), an inactive mutant of RAB-5 that reduces endocytosis, mimics the effect of pmk-3 mutations when introduced into wild-type animals, and occludes the effect of pmk-3 mutations when introduced into pmk-3 mutants. By contrast, RAB-5(GTP), which increases endocytosis, suppresses the effect of pmk-3 mutations, mimics the effect of rpm-1 mutations, and occludes the effect of rpm-1 mutations. Our findings indicate a novel specialized role for RPM-1 and PMK-3/p38 MAPK in regulating the endosomal trafficking of AMPARs at central synapses. 相似文献