全文获取类型
收费全文 | 268篇 |
免费 | 22篇 |
国内免费 | 10篇 |
专业分类
300篇 |
出版年
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 18篇 |
2014年 | 17篇 |
2013年 | 12篇 |
2012年 | 12篇 |
2011年 | 17篇 |
2010年 | 13篇 |
2009年 | 10篇 |
2008年 | 8篇 |
2007年 | 8篇 |
2006年 | 17篇 |
2005年 | 2篇 |
2004年 | 13篇 |
2003年 | 8篇 |
2002年 | 8篇 |
2001年 | 6篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 12篇 |
1992年 | 4篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1955年 | 1篇 |
1954年 | 2篇 |
排序方式: 共有300条查询结果,搜索用时 13 毫秒
51.
Ana Leonor Rivera Bruno Esta?ol Horacio Sentíes-Madrid Ruben Fossion Juan C. Toledo-Roy Joel Mendoza-Temis Irving O. Morales Emmanuel Landa Adriana Robles-Cabrera Rene Moreno Alejandro Frank 《PloS one》2016,11(2)
Diabetes Mellitus (DM) affects the cardiovascular response of patients. To study this effect, interbeat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) variability of patients during supine, standing and controlled breathing tests were analyzed in the time domain. Simultaneous noninvasive measurements of IBI and SBP for 30 recently diagnosed and 15 long-standing DM patients were compared with the results for 30 rigorously screened healthy subjects (control). A statistically significant distinction between control and diabetic subjects was provided by the standard deviation and the higher moments of the distributions (skewness, and kurtosis) with respect to the median. To compare IBI and SBP for different populations, we define a parameter, α, that combines the variability of the heart rate and the blood pressure, as the ratio of the radius of the moments for IBI and the same radius for SBP. As diabetes evolves, α decreases, standard deviation of the IBI detrended signal diminishes (heart rate signal becomes more “rigid”), skewness with respect to the median approaches zero (signal fluctuations gain symmetry), and kurtosis increases (fluctuations concentrate around the median). Diabetes produces not only a rigid heart rate, but also increases symmetry and has leptokurtic distributions. SBP time series exhibit the most variable behavior for recently diagnosed DM with platykurtic distributions. Under controlled breathing, SBP has symmetric distributions for DM patients, while control subjects have non-zero skewness. This may be due to a progressive decrease of parasympathetic and sympathetic activity to the heart and blood vessels as diabetes evolves. 相似文献
52.
Tyrosine phosphorylation of Munc18‐1 inhibits synaptic transmission by preventing SNARE assembly
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Marieke Meijer Bernhard Dörr Hanna CA Lammertse Chrysanthi Blithikioti Jan RT van Weering Ruud FG Toonen Thomas H Söllner Matthijs Verhage 《The EMBO journal》2018,37(2):300-320
Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18‐1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho‐proteomics abolished the stimulatory effect of Munc18‐1 on SNARE complex formation (“SNARE‐templating”) and membrane fusion in vitro. Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18‐1‐null neurons expressing Munc18‐1Y473D. Synaptic transmission was temporarily restored by high‐frequency stimulation, as well as by a Munc18‐1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming. On the other hand, expression of non‐phosphorylatable Munc18‐1 supported normal synaptic transmission. We propose that SFK‐dependent Munc18‐1 phosphorylation may constitute a potent, previously unknown mechanism to shut down synaptic transmission, via direct occlusion of a Synaptobrevin/VAMP2 binding groove and subsequent hindrance of conformational changes in domain 3a responsible for vesicle priming. This would strongly interfere with the essential post‐docking SNARE‐templating role of Munc18‐1, resulting in a largely abolished pool of releasable synaptic vesicles. 相似文献
53.
54.
Parthenogenetically activated, in vitro-matured bovine oocytes and parthenogenotes obtained at 2 to 4 days post activation were analyzed by 3H-thymidine autoradiography for the timing of the S-phase and for distribution of newly replicated DNA, respectively. Spread pronuclear parthenogenotes revealed that the DNA synthesis in electrically stimulated oocytes commenced at 14 h post activation. At 20 to 24 h, a maximum number of labeled pronuclei was reached (25 to 38%), and DNA synthesis persisted in some parthenogenotes up to 30 h post activation. The DNA labeling detected on semi-thin sections showed that the distribution of newly synthesized DNA in the nuclei of 3- to 16-cell parthenogenotes was mostly irregular or abnormal, documenting that the apparent morphological normalcy of parthenogenotes was in contrast to the data concerning the DNA synthesis and distribution. 相似文献
55.
铁皮石斛的离体开花 总被引:9,自引:0,他引:9
铁皮石斛(Dendrobium candidum),为一种野生兰科植物,在栽培条件下,从种子萌发到开花通常需要3~4a.研究了多种植物激素和多胺对该种石斛组织培养中花芽形成的影响,结果表明在培养基中加入合适浓度的亚精胺(spermidine)或BA(6-苄基腺嘌呤),或同时加入NAA(萘乙酸)和BA均可诱导原球茎或由之形成的无根小苗在3~6个月开花,频率在31.6%~45.8%.当将原球茎在加有ABA(脱落酸)的培养基上预培养后再移到加有BA的培养基上,花芽形成的频率可提高到平均达82.8%(个别实验中可达100%),这种诱导提早开花的现象也与实验材料的发育阶段(原球茎、无根小苗、已生根的小苗)有关,通常发生在根的形成受到完全或部分抑制的情况中. 相似文献
56.
57.
Efficiencies of different genes and different tree-building methods in recovering a known vertebrate phylogeny 总被引:24,自引:6,他引:18
The relative efficiencies of different protein-coding genes of the
mitochondrial genome and different tree-building methods in recovering a
known vertebrate phylogeny (two whale species, cow, rat, mouse, opossum,
chicken, frog, and three bony fish species) was evaluated. The
tree-building methods examined were the neighbor joining (NJ), minimum
evolution (ME), maximum parsimony (MP), and maximum likelihood (ML), and
both nucleotide sequences and deduced amino acid sequences were analyzed.
Generally speaking, amino acid sequences were better than nucleotide
sequences in obtaining the true tree (topology) or trees close to the true
tree. However, when only first and second codon positions data were used,
nucleotide sequences produced reasonably good trees. Among the 13 genes
examined, Nd5 produced the true tree in all tree-building methods or
algorithms for both amino acid and nucleotide sequence data. Genes Cytb and
Nd4 also produced the correct tree in most tree-building algorithms when
amino acid sequence data were used. By contrast, Co2, Nd1, and Nd41 showed
a poor performance. In general, large genes produced better results, and
when the entire set of genes was used, all tree-building methods generated
the true tree. In each tree-building method, several distance measures or
algorithms were used, but all these distance measures or algorithms
produced essentially the same results. The ME method, in which many
different topologies are examined, was no better than the NJ method, which
generates a single final tree. Similarly, an ML method, in which many
topologies are examined, was no better than the ML star decomposition
algorithm that generates a single final tree. In ML the best substitution
model chosen by using the Akaike information criterion produced no better
results than simpler substitution models. These results question the
utility of the currently used optimization principles in phylogenetic
construction. Relatively simple methods such as the NJ and ML star
decomposition algorithms seem to produce as good results as those obtained
by more sophisticated methods. The efficiencies of the NJ, ME, MP, and ML
methods in obtaining the correct tree were nearly the same when amino acid
sequence data were used. The most important factor in constructing reliable
phylogenetic trees seems to be the number of amino acids or nucleotides
used.
相似文献
58.
The enzyme xylonase was used to isolate the protoplasts from the leaves ofCalendula officinalis L.,Gazania splendens Moore,Tithonia rotundifolia Blake,Zinnia elegans Jacq- and from the petals ofDahlia variabilis (Willd.) Desf. The recovery of spherical undamaged protoplasts differed. The same method did not lead to the isolation of the protoplasts from callus cultures derived fromCalendula, Gazania andTithonia leaves respectively. 相似文献
59.
Formation of stems both in callus tissue isolated from hypocotyl and in apical meristems culture of carnation plants (Dianthus caryophyllus L. ev. “Grenadin white, yellow, scarlet red, dark red and pink”) was evokedin vitro using chemically defined medium. The rooted stems were transferred into pots and cultivated under natural conditions. 相似文献
60.
Cholinergic Neuronotrophic Factors: Fractionation Properties of an Extract from Selected Chick Embryonic Eye Tissues 总被引:7,自引:1,他引:6
Marston Manthorpe Stephen Skaper Ruben Adler Keith Landa Silvio Varon 《Journal of neurochemistry》1980,34(1):69-75
Abstract: An aqueous extract derived from selected intraocular tissues of 15-day chick embryos contains a soluble macromolecular agent which is capable of ensuring the survival of 8-day chick embryonic ciliary ganglionic neurons in monolayer culture. When this ciliary neuronotrophic factor (CNTF) was concentrated using ultrafiltration and subjected to Sephadex G100 and G200 chromatography, activity was detected in most of the eluted fractions. A peak of the most active fractions was eluted in a region corresponding to a molecular weight of 35–40 ± 103 and contained about 20-30% of the applied protein. CNTF activity bound readily to DE-52 cellulose resin at neutral pH and was eluted with NaCl in a narrow region containing about 20-40% of the applied protein. Gel electrophoretic staining profiles of the active DE52 fraction indicated considerable (but still only partial) simplification in protein composition. While significant CNTF activity losses were incurred in response to each of the above treatments, an active material could be conveniently generated in one working day in milligram amounts having a specific activity of 60,000 trophic units/mg protein. This trophic activity is in the same range as that of the only other known neuronotrophic factor, Nerve Growth Factor. 相似文献