全文获取类型
收费全文 | 6185篇 |
免费 | 758篇 |
国内免费 | 4篇 |
出版年
2023年 | 44篇 |
2022年 | 68篇 |
2021年 | 128篇 |
2020年 | 77篇 |
2019年 | 91篇 |
2018年 | 109篇 |
2017年 | 90篇 |
2016年 | 150篇 |
2015年 | 262篇 |
2014年 | 297篇 |
2013年 | 325篇 |
2012年 | 454篇 |
2011年 | 441篇 |
2010年 | 241篇 |
2009年 | 232篇 |
2008年 | 299篇 |
2007年 | 318篇 |
2006年 | 280篇 |
2005年 | 266篇 |
2004年 | 237篇 |
2003年 | 233篇 |
2002年 | 235篇 |
2001年 | 66篇 |
2000年 | 49篇 |
1999年 | 80篇 |
1998年 | 75篇 |
1997年 | 53篇 |
1996年 | 71篇 |
1995年 | 55篇 |
1992年 | 47篇 |
1991年 | 51篇 |
1990年 | 60篇 |
1989年 | 56篇 |
1988年 | 50篇 |
1987年 | 46篇 |
1986年 | 43篇 |
1985年 | 56篇 |
1984年 | 64篇 |
1983年 | 57篇 |
1982年 | 58篇 |
1981年 | 63篇 |
1980年 | 48篇 |
1979年 | 54篇 |
1978年 | 46篇 |
1977年 | 44篇 |
1976年 | 50篇 |
1974年 | 49篇 |
1973年 | 56篇 |
1972年 | 45篇 |
1969年 | 44篇 |
排序方式: 共有6947条查询结果,搜索用时 15 毫秒
61.
The soluble form of human brain catechol-O-methyltransferase (EC 2.1.1.6, COMT) has been purified approximately 4,000-fold from a 250,000 X g supernatant solution. The purified enzyme exhibits a molecular weight near 27,500 and a pI value equal to approximately pH 5.0. Initial velocity and product inhibition studies are consistent with an ordered reaction mechanism for soluble COMT. Tropolone, a dead-end inhibitor, exhibited a competitive pattern of inhibition when dopamine (DA) was the varied substrate and an uncompetitive pattern when S-adenosyl-L-methionine (SAM) was the varied substrate. These observations strongly suggest that the soluble form of COMT from human brain catalyzes the O-methylation of catecholamines via an ordered reaction mechanism in which SAM is the leading substrate. Since the membrane-bound form of COMT catalyzes the O-methylation of catecholamines through an identical reaction mechanism, these data provide further evidence that two forms of COMT, while being localized in distinct subcellular compartments, are quite similar in their molecular structure. 相似文献
62.
63.
Summary Highly sensitive and specific synthetic substrates were used to quantitate cathepsin B and D activity in peritoneal macrophages in response to stimulation in vivo with mineral oil and thioglycollate. After intraperitoneal instillation of mineral oil the activity of cathepsin B increased significantly (to 15 300 units/mg protein versus 7 340 in saline controls), reaching values approaching those found in alveolar macrophages (18 400 units/mg protein). Significantly greater stimulation of enzyme activity was obtained after intraperitoneal instillation of thioglycollate (23 600 units/mg protein). Cathepsin D activity also increased significantly after both mineral oil and thioglycollate. However, the increase was moderate (from 806 to about 1 200 units/mg protein), remaining still more than six times lower-than in alveolar macrophages. The data are the first to demonstrate that cathepsin B activity can be stimulated in vivo in peritoneal macrophages by instillation of agents that induce acute inflammation. They also point to a differential control of expression of cathepsin B and D activity in both peritoneal and alveolar macrophages in spite of the common lysosomal origin of the two enzymes.Abbreviations Cbz
-N-benxyloxycarbonyl
- 2NA
2-naphthylamine
- EDTA
ethylenediamine tetraacetate
- DMSO
dimethylsulfoxide
- PBS
phosphate-buffered saline
- PM
peritoneal macrophage
- AM
alveolar macrophage 相似文献
64.
Some males of a mutant strain of King-Holtzman rats exhibit an anomalous heritable defect manifested as either unilateral or bilateral ectopic testes. In the adult, these testes contain seemingly immature Sertoli and Leydig cells, seminiferous tubules greatly reduced in diameter, and exhibit arrested spermatogenesis. Thus, the affected testis is essentially sterile. An inability to produce normal amounts of testosterone and androstenedione by these gonads is probably a reflection of changes that have been effected in their Leydig cells. Thus, this study suggests that abnormal function of the Leydig and Sertoli cells and seminiferous tubule failure in these mutant animals result from the physiologically cryptorchid condition. 相似文献
65.
Characterization of Membrane-Bound and Soluble Catechol-O-Methyltransferase from Human Frontal Cortex 总被引:4,自引:3,他引:1
Abstract: Catechol- O -methyltransferase (COMT; E.C. 2.1.1.6) from human frontal cortex occurs in both a soluble and membrane-bound form. Attempts to solubilize the membrane-bound transferase by repeated washing or by extraction into solutions of high ionic strength were unsuccessful. The finding that Triton X-100 was capable of solubilizing membrane-bound COMT suggested that the membrane-bound transferase is an integral membrane protein. The membrane-bound and soluble enzymes did not differ in their requirements for magnesium ions or in their pH-activity profiles; both enzymes showed an optimum near pH 8.0 when assayed in phosphate buffer. In addition, the two enzymes did not differ in the degree of inhibition caused by CaCl2 , both enzymes displaying 65% inhibition at 2.5 m M CaCl2 . The competitive inhibitors tropolone and nordihydroguaiaretic acid displayed K i values for the membrane-bound transferase five- to 10-fold lower than those observed for the soluble transferase. Solubilization of membrane-bound COMT in Triton X-100 resulted in an increase in the apparent K m value of the membrane-bound transferase for dopamine. The increase in K m appeared to be due to apparent competitive inhibition by Triton X-100 and reached a limiting value of approximately 80 μM. These results confirm that membrane-bound COMT is an integral membrane protein that may be structurally distinct from soluble COMT. 相似文献
66.
Glucocorticoid-Induced Cleft Palate in the Mouse: Two Major Histocompatibility Complex, H-2, Loci with Different Mechanisms 总被引:1,自引:0,他引:1 下载免费PDF全文
Isolated cleft palate is induced in the progeny of pregnant mice that are given glucocorticoids. The incidence varies among inbred strains and with dose and stage of gestation when the drug is given. One chromosomal region responsible for strain-associated differences in sensitivity is the major histocompatibility complex, H-2. H-2a is associated with susceptibility, H-2b with resistance. There appear to be both maternal and embryonic genetic factors affecting the sensitivity to glucocorticoids. In experiments reported here congenic strains of mice with H-2a, H-2d and H-2k haplotypes on a C57BL/10 genomic background were used. This allowed the determination of the effect on sensitivity by two H-2 subregions; the subregions are H-2K to I-E and I-C to H-2D. Methods included dose-response analysis and reciprocal cross analysis using dexamethasone given on day 12 of pregnancy. Results show that each subregion affects the strain's sensitivity to dexamethasone-induced cleft palate. The regression coefficients for B10.A-H-2a (45.4 ± 4.13) were different from those for B10.BR-H-2k (67.2 ± 10.8) and B10.D2-H-2d (70.5 ± 9.74). The estimated mean arcsine% cleft palate at 160 mg/kg was different for each strain: B10.A- H-2a, 53.1 ± 2.19; B10.BR-H-2k, 33.1 ± 2.27; B10.D2-H-2d, 25.0 ± 2.75. Different patterns of change in sensitivity were observed among the reciprocal crosses. In summary, the H-2K to I-E subregion seemed to influence both maternal and embryonic factors, whereas only embryonic factors were influenced by the I-C to H-2D subregion. These data suggest that the mechanisms affecting glucocorticoid sensitivity which are genetically encoded within each H-2 subregion are different, and there is an interaction between the alleles. The mode of interaction can be either complementation or epistasis. 相似文献
67.
Proton-translocating ATPase and lysosomal cystine transport 总被引:6,自引:0,他引:6
A J Jonas M L Smith W S Allison P K Laikind A A Greene J A Schneider 《The Journal of biological chemistry》1983,258(19):11727-11730
A proton-translocating ATPase was identified in highly purified lysosomes from Epstein-Barr virus-transformed human lymphoblasts. Activity of this ATPase caused acidification of highly purified, fluorescein isothiocyanate dextran-loaded lysosomes and correlated with the ATP-dependent efflux of lysosomal cystine. The lysosomal ATPase was distinct from mitochondrial F1-ATPase in its responses to a variety of inhibitors. Although ATP-dependent lysosomal cystine efflux is not demonstrable in cultured lymphoblasts from individuals with nephropathic cystinosis, ATPase activity and acidification in lysosomes from these cells is comparable to that in noncystinotic lysosomes. ATPase activity in lymphoblasts from normal individuals was 543 +/- 79 nmol/mg/min while in lymphoblasts from cystinotic individuals this activity was 541 +/- 25 nmol/mg/min. ATP-dependent acidification of lysosomes from normals was -0.5 +/- 0.1 pH units compared to -0.5 +/- 0.1 pH units in cystinotic lysosomes. Activity of the lysosomal proton-translocating ATPase is a necessary, but not sufficient, condition for lysosomal cystine efflux. 相似文献
68.
Marvin R. Mark Edward F. Domino Seong S. Han Aurelio Ortiz Benjamin N. Mathews Sandra K. Tait 《Life sciences》1983,33(12):1191-1197
Parasympathetic denervation of the rat parotid gland by avulsion of the auriculotemporal nerve caused a marked and lasting decrease in gland weight. Parasympathectomy did not change the levels of choline in the gland but decreased by 60% the levels of acetylcholine (ACh) ten days after surgery and 65% at 28 days. It is puzzling that relatively high levels of ACh remained after parasympathetic denervation. The presence of additional cholinergic nerves that innervate the gland, or pass through it en route to other structures may account for some of the remaining ACh. Also, Schwann cells from denervated nerves might have contributed to some of the ACh. The existence of an extraneuronal source of ACh is considered. 相似文献
69.
70.