全文获取类型
收费全文 | 3932篇 |
免费 | 261篇 |
国内免费 | 2篇 |
专业分类
4195篇 |
出版年
2022年 | 14篇 |
2021年 | 38篇 |
2020年 | 23篇 |
2019年 | 30篇 |
2018年 | 47篇 |
2017年 | 54篇 |
2016年 | 76篇 |
2015年 | 117篇 |
2014年 | 141篇 |
2013年 | 206篇 |
2012年 | 208篇 |
2011年 | 236篇 |
2010年 | 153篇 |
2009年 | 139篇 |
2008年 | 195篇 |
2007年 | 212篇 |
2006年 | 220篇 |
2005年 | 203篇 |
2004年 | 228篇 |
2003年 | 225篇 |
2002年 | 229篇 |
2001年 | 108篇 |
2000年 | 95篇 |
1999年 | 86篇 |
1998年 | 52篇 |
1997年 | 49篇 |
1996年 | 41篇 |
1995年 | 34篇 |
1994年 | 36篇 |
1993年 | 25篇 |
1992年 | 65篇 |
1991年 | 48篇 |
1990年 | 38篇 |
1989年 | 47篇 |
1988年 | 37篇 |
1987年 | 47篇 |
1986年 | 38篇 |
1985年 | 53篇 |
1984年 | 44篇 |
1983年 | 31篇 |
1982年 | 19篇 |
1981年 | 20篇 |
1980年 | 16篇 |
1979年 | 25篇 |
1978年 | 13篇 |
1976年 | 11篇 |
1975年 | 15篇 |
1974年 | 14篇 |
1972年 | 14篇 |
1971年 | 11篇 |
排序方式: 共有4195条查询结果,搜索用时 15 毫秒
1.
We have previously shown that replacing the P1-site residue (Ala) of chicken ovomucoid domain 3 (OMCHI3) with a Met or Lys results in the acquisition of inhibitory activity toward chymotrypsin or trypsin, respectively. However, the inhibitory activities thus induced are not strong. In the present study, we introduced additional amino acid replacements around the reactive site to try to make the P1-site mutants more effective inhibitors of chymotrypsin or trypsin. The amino acid replacement Asp-->Tyr at the P2' site of OMCHI3(P1Met) resulted in conversion to a 35000-fold more effective inhibitor of chymotrypsin with an inhibitor constant (K(i)) of 1. 17x10(-11) M. The K(i) value of OMCHI3(P1Met, P2'Ala) indicated that the effect on the interaction with chymotrypsin of removing a negative charge from the P2' site was greater than that of introducing an aromatic ring. Similarly, enhanced inhibition of trypsin was observed when the Asp-->Tyr replacement was introduced into the P2' site of OMCHI3(P1Lys). Two additional replacements, Asp-->Ala at the P4 site and Arg-->Ala at the P3' site, made the mutant a more effective inhibitor of trypsin with a K(i) value of 1. 44x10(-9) M. By contrast, Arg-->Ala replacement at the P3' site of OMCHI3(P1Met, P2'Tyr) resulted in a greatly reduced inhibition of chymotrypsin, and Asp-->Ala replacement at the P4 site produced only a small change when compared with a natural variant of OMCHI3. These results clearly indicate that not only the P1-site residue but also the characteristics, particularly the electrostatic properties, of the amino acid residues around the reactive site of the protease inhibitor determine the strength of its interactions with proteases. Furthermore, amino acids with different characteristics are required around the reactive site for strong inhibition of chymotrypsin and trypsin. 相似文献
2.
3.
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
4.
Centrifugal filtration through a double layer of silicone oil was applied to determine the intermembrane space of organelles enclosed by double envelope membranes, i.e. proplastids, chloroplasts, mitochondria and amyloplasts. The organelles, capable of transporting adenylates by an adenylate translocator located in the inner envelope membrane, were incubated with increasing concentrations of adenylates while maintaining their specific radioactivities constant. Intermembrane spaces were estimated by extrapolation of radioactivities recovered after filtration of the organelles. The values estimated were compared to those obtained employing the classical method measuring the intake of [14C]-sucrose and [14C]-sorbitol which are impermeable to the inner membranes of organelles. The intermembrane space determined by the present method was shown to be uniformly smaller than the sucrose-permeable space which was always smaller than the sorbitol-permeable space. 相似文献
5.
The axial growth of de-coated cocklebur (Xanthium pennsylvanicumWallr.) seeds, whose axes were divided into 4 zones, was examinedin relation to the temperature-dependent shift of the effectof C2H4 on germination. At 23?C, where both C2H4 and CO2 stimulatedgermination, CO2 promoted the axial growth at the radicle tipzone, whereas C2H4 promoted growth in the proximal portion ofthe axis. At 33?C, C2H4 inhibited germination, and stronglysuppressed the growth at the radicle tip, whereas the effectof CO2 did not change. The inhibition of growth at the radicletip zone was alleviated by O2 enrichment, which also reversedthe inhibition of germination. It is thus apparent that thetemperature-dependent shift of the action of C2H4 is associatedwith a temperature-dependent responsiveness of the radicle tipzone to C2H4. Growth of the radicle tip zone was sensitive toNaN3, whereas the proximal portion was sensitive to benzohydroxamicacid, an inhibitor of alternative respiration, suggesting thatthere may be an increase in the operation of the alternativerespiration path along a gradient of axial tissue from the tiptowards the cotyledonary side. The effects of CO2 and C2H4 arediscussed in relation to the different respiratory activitiesin each axial zone of cocklebur seeds. (Received May 9, 1986; Accepted November 6, 1986) 相似文献
6.
Primary structures of two types of alpha-subunit of rat brain Na+,K+,-ATPase deduced from cDNA sequences 总被引:2,自引:0,他引:2
Y Hara O Urayama K Kawakami H Nojima H Nagamune T Kojima T Ohta K Nagano M Nakao 《Journal of biochemistry》1987,102(1):43-58
A rat brain cDNA library was screened by using as a probe a fragment of cDNA encoding the alpha-subunit of human Na+,K+-ATPase. Two different cDNA clones were obtained and analyzed. One of them was concluded to be a cDNA encoding the alpha-subunit of the weakly ouabain-sensitive rat kidney-type Na+,K+-ATPase. The deduced amino acid sequence consists of 1,018 amino acids. The alpha-subunit of the rat kidney-type Na+,K+-ATPase shows 97% homology in amino acid sequence with the alpha-subunit of human, sheep, or pig enzyme and 87% with that of Torpedo. Based on a comparison of the amino acid sequence at the extracellular domain of the alpha-subunit between weakly ouabain-sensitive rat kidney-type enzyme and the ouabain-sensitive human, sheep, pig, or Torpedo enzyme, it was proposed that only two significant amino acid replacements are unique to the rat kidney-type alpha-subunit. Another cDNA clone obtained showed 72% homology in nucleotide sequence with the former cDNA coding the alpha-subunit of the rat kidney-type Na+,K+-ATPase and the deduced amino acid sequence exhibited 85% homology with that of the alpha-subunit of rat kidney-type Na+,K+-ATPase. 相似文献
7.
Porcine polymorphonuclear leukocyte NADPH-cytochrome c reductase generates superoxide in the presence of cytochrome b559 and phospholipid 总被引:1,自引:0,他引:1
F Sakane H Kojima K Takahashi J Koyama 《Biochemical and biophysical research communications》1987,147(1):71-77
NADPH-cytochrome c reductase and cytochrome b559 were purified from the membrane fraction of phorbol myristate acetate-stimulated porcine polymorphonuclear leukocytes. The highly purified reductase oxidized NADPH and generated superoxide when combined with partially purified cytochrome b559 in the presence of phosphatidylcholine. In the same system, but under the anaerobic condition, the reductase was found to reduce cytochrome b559. 相似文献
8.
Y Inada K Ohwada T Yoshimoto S Kojima K Takahashi Y Kodera A Matsushima Y Saito 《Biochemical and biophysical research communications》1987,148(1):392-396
The activated magnetic modifier was synthesized from magnetite, alpha, omega-dicarboxymethylpoly(oxyethylene) and N-hydroxysuccinimide (Biochem. Biophys. Res. Commun., 145, 908-914, 1987). Urokinase was directly coupled with the activated magnetic modifier to obtain magnetic urokinase. The magnetic urokinase dispersed in saline and exerted high fibrinolytic activity (13.8 X 10(4) IU/mg protein), and was readily recovered from saline by magnetic force of 250 Oe. By applying magnetic force, the urokinase was attracted at our will and local fibrinolysis was achieved on fibrin gel in a petri dish. 相似文献
9.
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
10.