全文获取类型
收费全文 | 3507篇 |
免费 | 231篇 |
国内免费 | 1篇 |
专业分类
3739篇 |
出版年
2022年 | 19篇 |
2021年 | 33篇 |
2020年 | 20篇 |
2019年 | 33篇 |
2018年 | 47篇 |
2017年 | 51篇 |
2016年 | 78篇 |
2015年 | 109篇 |
2014年 | 128篇 |
2013年 | 170篇 |
2012年 | 191篇 |
2011年 | 206篇 |
2010年 | 141篇 |
2009年 | 121篇 |
2008年 | 163篇 |
2007年 | 189篇 |
2006年 | 209篇 |
2005年 | 183篇 |
2004年 | 218篇 |
2003年 | 212篇 |
2002年 | 209篇 |
2001年 | 68篇 |
2000年 | 60篇 |
1999年 | 77篇 |
1998年 | 56篇 |
1997年 | 47篇 |
1996年 | 32篇 |
1995年 | 31篇 |
1994年 | 38篇 |
1993年 | 17篇 |
1992年 | 41篇 |
1991年 | 39篇 |
1990年 | 41篇 |
1989年 | 42篇 |
1988年 | 43篇 |
1987年 | 45篇 |
1986年 | 33篇 |
1985年 | 35篇 |
1984年 | 31篇 |
1983年 | 33篇 |
1982年 | 24篇 |
1981年 | 14篇 |
1980年 | 18篇 |
1979年 | 15篇 |
1978年 | 15篇 |
1977年 | 18篇 |
1976年 | 14篇 |
1975年 | 17篇 |
1974年 | 10篇 |
1972年 | 8篇 |
排序方式: 共有3739条查询结果,搜索用时 15 毫秒
1.
Julie A. Harris Akihiko Koyama Sumihiro Maeda Kaitlyn Ho Nino Devidze Dena B. Dubal Gui-Qiu Yu Eliezer Masliah Lennart Mucke 《PloS one》2012,7(9)
Accumulation of hyperphosphorylated tau in the entorhinal cortex (EC) is one of the earliest pathological hallmarks in patients with Alzheimer’s disease (AD). It can occur before significant Aβ deposition and appears to “spread” into anatomically connected brain regions. To determine whether this early-stage pathology is sufficient to cause disease progression and cognitive decline in experimental models, we overexpressed mutant human tau (hTauP301L) predominantly in layer II/III neurons of the mouse EC. Cognitive functions remained normal in mice at 4, 8, 12 and 16 months of age, despite early and extensive tau accumulation in the EC. Perforant path (PP) axon terminals within the dentate gyrus (DG) contained abnormal conformations of tau even in young EC-hTau mice, and phosphorylated tau increased with age in both the EC and PP. In old mice, ultrastructural alterations in presynaptic terminals were observed at PP-to-granule cell synapses. Phosphorylated tau was more abundant in presynaptic than postsynaptic elements. Human and pathological tau was also detected within hippocampal neurons of this mouse model. Thus, hTauP301L accumulation predominantly in the EC and related presynaptic pathology in hippocampal circuits was not sufficient to cause robust cognitive deficits within the age range analyzed here. 相似文献
2.
Hironori Hirata 《Bulletin of mathematical biology》1982,44(5):697-704
This paper has studied the evolution of a predator-prey Volterra-Lotka ecosystem with saturation effect for the general case
where both predator and prey evolve. We have interesting results under the evolutional condition, as follows: (1) the predator
population and the ratio of predator to prey populations increase; (2) the parameters of the prey drift in the direction of
increasing multiplication rate and saturation level, while the parameters of the predator drift in the direction of decreasing
death rate. 相似文献
3.
Human and nonhuman primates comprehend the actions of other individuals by detecting social cues, including others’ goal-directed motor actions and faces. However, little is known about how this information is integrated with action understanding. Here, we present the ontogenetic and evolutionary foundations of this capacity by comparing face-scanning patterns of chimpanzees and humans as they viewed goal-directed human actions within contexts that differ in whether or not the predicted goal is achieved. Human adults and children attend to the actor’s face during action sequences, and this tendency is particularly pronounced in adults when observing that the predicted goal is not achieved. Chimpanzees rarely attend to the actor’s face during the goal-directed action, regardless of whether the predicted action goal is achieved or not. These results suggest that in humans, but not chimpanzees, attention to actor’s faces conveying referential information toward the target object indicates the process of observers making inferences about the intentionality of an action. Furthermore, this remarkable predisposition to observe others’ actions by integrating the prediction of action goals and the actor’s intention is developmentally acquired. 相似文献
4.
Daisuke Hirata Alexei V. Abramov Gennady F. Baryshnikov Ryuichi Masuda 《Biological journal of the Linnean Society. Linnean Society of London》2014,111(3):627-635
Sequence analyses of the complete brown bear, Ursus arctos, mitochondrial DNA (mtDNA) genome have detected scattered single nucleotide polymorphisms (SNPs) that define distinct mtDNA haplogroups in phylogeographical studies. The degraded DNA in historical samples, such as stuffed or excavated specimens, however, is often not suitable for sequence analyses. To address this problem, we developed an amplified product length polymorphism (APLP) analysis for mtDNA‐haplogrouping U. arctos specimens by detecting haplogroup‐specific SNPs. We verified the validity and utility of this method by analysing up to 170‐year‐old skin samples from U. arctos specimens collected widely across continental Eurasia. We detected some of the same haplogroups as those occurring in eastern Hokkaido (Japan) and eastern Alaska in continental Eurasia (the Altai and the Caucasus). Our results show that U. arctos in eastern Hokkaido and eastern Alaska descended from a common ancestor in continental Eurasia, and suggest that U. arctos occupied several refugia in southern Asia during the Last Glacial Maximum. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 111 , 627–635. 相似文献
5.
Structure and expression of cDNA for an inhibitor of blood coagulation isolated from human placenta: a new lipocortin-like protein 总被引:10,自引:0,他引:10
A Iwasaki M Suda H Nakao T Nagoya Y Saino K Arai T Mizoguchi F Sato H Yoshizaki M Hirata 《Journal of biochemistry》1987,102(5):1261-1273
An inhibitor of blood coagulation, a new protein with an apparent molecular weight of 34,000 and an isoelectric point of 4.9, was purified from human placental tissue by EDTA extraction. Five cDNA clones were isolated from the human placental lambda gt11 cDNA library using the mouse monoclonal antibody raised against the coagulation inhibitor as the probe. The longest insert consists of 1,566 nucleotides, and contains 960 nucleotides entirely encoding the 320 amino acids of the inhibitor, and a poly A tail. The deduced amino acid sequence was corroborated by chemical analyses of the protein. The entire amino acid sequence shows homology to those of lipocortin I, lipocortin II, and endonexin-related proteins. The cDNA for the inhibitor was expressed in Escherichia coli under the regulation of the trc promotor of the plasmid pKK233-2. The resulting recombinant protein manifested inhibitory activities against both blood coagulation and phospholipase A2 activity, as did the coagulation inhibitor isolated from human placenta. 相似文献
6.
Effects of calcium-antagonists and calmodulin inhibitors on DNA synthesis in cultured rat vascular smooth muscle cells 总被引:1,自引:0,他引:1
To investigate the role of intracellular Ca2+ in the mechanism of cellular proliferation of vascular smooth muscle cells (VSMC), the effects of Ca2+-antagonists and calmodulin (CaM) inhibitors on DNA synthesis stimulated by serum-derived growth factors were studied in cultured VSMCs derived from rat aorta. DNA synthesis assessed by incorporation of [3H]thymidine into the cells was significantly stimulated by epidermal growth factor (EGF), platelet-derived growth factor (PDGF) or fetal bovine serum (FBS), of which the effects were dose-dependently inhibited by a variety of Ca2+-antagonists, such as verapamil, diltiazem and nicardipine. Trifluoperazine and W-7, both specific CaM inhibitors, similarly inhibited DNA synthesis stimulated by EGF, PDGF or FBS in a dose-dependent manner, whereas W-5, a less specific CaM inhibitor, was minimally effective. These data suggest that the Ca2+-CaM system plays an important role in the mechanism of growth factor-induced DNA synthesis in VSMCs. 相似文献
7.
James M. Mason Nita N. Scobie Akihiko H. Yamamoto 《Molecular & general genetics : MGG》1989,215(2):190-199
Summary The mutagen-sensitive mutant mus(1)104
D1
of Drosophila melanogaster maps to a position on the X chromosome very close to the meiotic mutant mei-41
D5
. Both mutants have been characterized as mutagen-sensitive and defective in post-replication repair. In the present report we show by complementation studies that mus(1)104 and mus(1)103 are allelic with mei-41. In addition, two reported alleles of mus(1)104 lie between the mei-41 alleles A10 and D5. The size of the mei-41 locus is estimated to be about 0.1 centimorgans (cM). Because several alleles of mei-41 have been shown to reduce recombination and increase meiotic chromosome loss and nondisjunction, mus(1)104
D1
females were examined for defects in meiosis. Although there was no evidence for reduced recombination on the second chromosome in homozygous mus(1)104
D1
females, heterozygous mus(1)104
D1
/mei-41
>D5
and mus(1)104
D1
/deficiency females showed reduced levels of recombination. However, there was no evidence of an increase in nondijunction in these females.We dedicate this article to the memory of Larry Sandler, who passed away suddenly on February 7, 1987 相似文献
8.
Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130 总被引:109,自引:0,他引:109
T Taga M Hibi Y Hirata K Yamasaki K Yasukawa T Matsuda T Hirano T Kishimoto 《Cell》1989,58(3):573-581
Interleukin-6 mediates pleiotropic functions in various types of cells through its specific receptor (IL-6-R), the cDNA of which has already been cloned. We report here that an 80 kd single polypeptide chain (IL-6-R) is involved in IL-6 binding and that IL-6 triggers the association of this receptor with a non-ligand-binding membrane glycoprotein, gp130. The association takes place at 37 degrees C within 5 min and is stable for at least 40 min in the presence of IL-6, but does not occur at 0 degree C. Human IL-6-R can associate with a murine gp130 homolog and is functional in murine cells. Mutant IL-6-R lacking the intracytoplasmic portion is functional, suggesting that the two polypeptide chains interact to involve their extracellular portion. In fact, a soluble IL-6-R lacking the transmembrane and intracytoplasmic domains can associate with gp130 in the presence of IL-6 and mediate its function. These findings indicate that the complex of IL-6 and IL-6-R can interact with a non-ligand-binding membrane glycoprotein, gp130, extracellularly and can provide the IL-6 signal. 相似文献
9.
The purpose of this study was to examine the possibility of separation and quantification of serum alkaline phosphatase (ALP) isozymes in rats by wheatgerm lectin affinity electrophoresis. Cellulose acetate electrophoresis of the liver and bone ALPs without lectin results in overlapping bands, but in the presence of lectin, the mobility of the band of bone enzyme was retarded and well separated from the liver enzyme band. With this affinity electrophoretic method, we determined the serum ALP isozymes in fed and fasting rats grouped by age. As a result, the absolute activity of bone isozyme showed a downward trend with age in the fed and fasting rats. The serum ALP activity was steadily higher in fed rats than in fasting rats, and the increase was due to intestinal ALP isozyme. There was low activity bordering complete absence in liver isozyme under both nutritional conditions. The affinity electrophoretic method provided a rapid, reproducible, and relatively simple technique for further clinical characterization of ALP isozyme in the rat serum. 相似文献
10.
The acid saline extract (ASE) of rat submaxillary gland exerts a powerful degrading effect on 125I-glucagon. In order to study the degradation of other 125I-peptides by ASE and the effects of their inhibitors, 125I-pancreatic polypeptide (PP) and 125I-insulin were used together with 125I-glucagon. The degradation studies were done by the trichloroacetic acid (TCA) method or gel filtration. Besides 125I-glucagon, 125I-PP was found to be destroyed by ASE in the ordinary immunoassay system using the TCA method, but 125I-insulin was intact in the presence of ASE. Leupeptin, and to a lesser extent p-chloromercuriphenyl-sulfonic acid (PCMS) and N-ethylmaleimide, inhibited the destruction of 125I-glucagon or -PP under the TCA method. PCMS was especially protective at high concentrations, for example 16 mM. These findings were confirmed by gel filtration of the assay mixture. In the presence of leupeptin (0.4 mM) and PCMS (16 mM), no shift in the peak of labelled glucagon or PP occurred. Thus ASE degrades not only 125I-glucagon but -PP, and thiol proteinase inhibitors have a strong inhibitory action on them. 相似文献