全文获取类型
收费全文 | 3151篇 |
免费 | 299篇 |
出版年
2022年 | 24篇 |
2021年 | 56篇 |
2020年 | 24篇 |
2019年 | 34篇 |
2018年 | 46篇 |
2017年 | 23篇 |
2016年 | 54篇 |
2015年 | 111篇 |
2014年 | 110篇 |
2013年 | 173篇 |
2012年 | 206篇 |
2011年 | 187篇 |
2010年 | 114篇 |
2009年 | 103篇 |
2008年 | 135篇 |
2007年 | 144篇 |
2006年 | 141篇 |
2005年 | 132篇 |
2004年 | 139篇 |
2003年 | 146篇 |
2002年 | 133篇 |
2001年 | 57篇 |
2000年 | 48篇 |
1999年 | 61篇 |
1998年 | 45篇 |
1997年 | 21篇 |
1996年 | 25篇 |
1995年 | 25篇 |
1994年 | 21篇 |
1993年 | 23篇 |
1992年 | 55篇 |
1991年 | 45篇 |
1990年 | 39篇 |
1989年 | 32篇 |
1988年 | 57篇 |
1987年 | 38篇 |
1986年 | 45篇 |
1985年 | 38篇 |
1984年 | 28篇 |
1983年 | 27篇 |
1982年 | 24篇 |
1981年 | 36篇 |
1980年 | 31篇 |
1979年 | 28篇 |
1978年 | 36篇 |
1977年 | 27篇 |
1976年 | 33篇 |
1975年 | 32篇 |
1974年 | 30篇 |
1972年 | 25篇 |
排序方式: 共有3450条查询结果,搜索用时 62 毫秒
81.
82.
W E Klunk J W Pettegrew D J Abraham 《The journal of histochemistry and cytochemistry》1989,37(8):1293-1297
Binding with low-affinity ligands, such as histological dyes, can be difficult to quantitate owing to the dissociation of bound ligand with washing or the retention of nonspecifically bound ligand because of incomplete washing. The present report describes two simple, rapid methods of discriminating bound from free ligand without the need for washing steps. One method is based on the spectral changes induced in a dye ligand, Congo red, on binding to the "receptor" insulin fibrils. This method discriminates spectrophotometrically between bound and free ligand without requiring any physical separation of the two forms. No radioactive ligands are necessary, and, by using disposable cuvettes, the entire binding assay can be done in a single container without the need for transfers. The second method employs a non-traditional filtration approach that avoids the need for a washing step by measuring the decrease in concentration of the dye ligand in the filtrate rather than by applying the usual approach of measuring the absolute amount of ligand bound to the precipitated "receptor." Both methods show saturation of binding sites and give similar values for the KD and Bmax. 相似文献
83.
Mariassy A. T.; Abraham W. M.; Phipps R. J.; Sielczak M. W.; Wanner A. 《Journal of applied physiology》1990,68(6):2504-2510
We determined whether exposure to O3 early in the postnatal period impairs the normal development of the mucociliary apparatus in lambs and whether such changes lead to prolonged abnormalities in mucociliary function. Lambs were exposed to air (controls) or to 1 ppm O3 for 4 h/day for 5 days during the 1st wk of life. Tracheal mucus velocity (TMV), a marker of lung mucociliary clearance, was measured in vivo at birth (0 wk) and up to 24 wk later, and tracheal secretory function was measured (in vitro) and the morphology of the tracheal mucosa was determined at 0 and 2 wk in both groups. In the control group, TMV increased 94% from 0 to 2 wk (P less than 0.05), continued to increase until reaching a plateau at 8 wk, and then remained constant from 8 to 24 wk. In contrast, O3-exposed lambs showed a 24% decrease in TMV from 0 to 2 wk (P less than 0.05 vs. control), and throughout the remaining time TMV remained below (P less than 0.05) that observed in control lambs. O3 exposure partially prevented the age-dependent decrease in basal secretion of tracheal macromolecules normally observed between 0 and 2 wk. These changes in secretory function were associated with a significant increase in tissue conductance (37%, P less than 0.05 vs. 0 wk), predominantly the result of active chloride secretion. The functional changes induced by O3 were associated with a retardation of the normal morphological development of the tracheal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
84.
Einat Sadot David Gurwitz Jacob Barg Leah Behar Irith Ginzburg †Abraham Fisher 《Journal of neurochemistry》1996,66(2):877-880
Abstract: Hyperphosphorylated τ proteins are the principal fibrous component of the neurofibrillary tangle pathology in Alzheimer's disease. The possibility that τ phosphorylation is controlled by cell surface neurotransmitter receptors was examined in PC12 cells transfected with the gene for the rat m1 muscarinic acetylcholine receptor. Stimulation of m1 receptor in these cells with two acetylcholine agonists, carbachol and AF102B, decreased τ phosphorylation, as indicated by specific τ monoclonal antibodies that recognize phosphorylation-dependent epitopes and by alkaline phosphatase treatment. The muscarinic effect was both time and dose dependent. In addition, a synergistic effect on τ phosphorylation was found between treatments with muscarinic agonists and nerve growth factor. These studies provide the first evidence for a link between the cholinergic signal transduction system and the neuronal cytoskeleton that can be mediated by regulated phosphorylation of τ microtubule-associated protein. 相似文献
85.
†Kelly J. Conn Michael Pietropaolo ‡Shyr-Te Ju † Carmela R. Abraham 《Journal of neurochemistry》1996,66(5):2011-2018
Abstract: Alzheimer's disease is characterized neuropathologically by the presence of neuritic and amyloid plaques, vascular amyloid, and neurofibrillary tangles in specific brain areas. The main constituent of amyloid deposits is amyloid β protein, a 40–42 amino acid proteolytic product of the amyloid β-precursor protein. In our search for proteases that can generate the N-terminus of amyloid β protein (β-secretases), we discovered a thiol-dependent metalloprotease that was identified, by peptide sequencing, as metalloendopeptidase EC 3.4.24.15. In vitro, the metalloprotease cleaves the methionine-aspartic acid bond in a 10 amino acid synthetic peptide, indicating that it could generate the N-terminus of amyloid β protein, and generates amyloidogenic fragments from full-length recombinant amyloid β-precursor protein. Mouse monoclonal antibodies produced against a unique synthetic peptide from the metalloprotease labeled various monkey tissues as detected by western blots and immunohistochemistry. Unexpectedly, two monoclonal antibodies, IVD6 and IIIF3, immunolabeled strongly intracellular neurofibrillary tangles, neurites of senile plaques, and neuropil threads, but not "ghost" tangles or amyloid in sections taken from Alzheimer's disease brain. This finding provides further evidence for the metalloprotease's relevance to Alzheimer's disease pathology, although the connection between tangle staining and the formation of amyloid β protein remains to be elucidated. 相似文献
86.
Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. 总被引:31,自引:2,他引:29
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)
G J Brunn J Williams C Sabers G Wiederrecht J C Lawrence Jr R T Abraham 《The EMBO journal》1996,15(19):5256-5267
The immunosuppressant, rapamycin, inhibits cell growth by interfering with the function of a novel kinase, termed mammalian target of rapamycin (mTOR). The putative catalytic domain of mTOR is similar to those of mammalian and yeast phosphatidylinositol (PI) 3-kinases. This study demonstrates that mTOR is a component of a cytokine-triggered protein kinase cascade leading to the phosphorylation of the eukaryotic initiation factor-4E (eIF-4E) binding protein, PHAS-1, in activated T lymphocytes. This event promotes G1 phase progression by stimulating eIF-4E-dependent translation initiation. A mutant YAC-1 T lymphoma cell line, which was selected for resistance to the growth-inhibitory action of rapamycin, was correspondingly resistant to the suppressive effect of this drug on PHAS-1 phosphorylation. In contrast, the PI 3-kinase inhibitor, wortmannin, reduced the phosphorylation of PHAS-1 in both rapamycin-sensitive and -resistant T cells. At similar drug concentrations (0.1-1 microM), wortmannin irreversibly inhibited the serine-specific autokinase activity of mTOR. The autokinase activity of mTOR was also sensitive to the structurally distinct PI 3-kinase inhibitor, LY294002, at concentrations (1-30 microM) nearly identical to those required for inhibition of the lipid kinase activity of the mammalian p85-p110 heterodimer. These studies indicate that the signaling functions of mTOR, and potentially those of other high molecular weight PI 3-kinase homologs, are directly affected by cellular treatment with wortmannin or LY294002. 相似文献
87.
Near-isogenic wheat lines differing in height-reducing (Rht) alleles, in each of two cultivars, were used to investigate the effects of light intensity and of their interaction with temperature and GA3 application, on the elongation of the coleoptile and the first seedling leaf. Darkness caused a conspicuous increase in the lengths of the coleoptile and of the sheath and lamina of the first leaf, in GA3 treated and untreated seedlings of all genotypes grown at 11 and 25°C. The genotype effects and the effects of light intensity and GA3 application on leaf length were ascribed entirely to their effects on the rate of leaf elongation since the duration of leaf elongation was not affected by these factors. Temperature elevation from 11 to 25°C caused a 55% shortening of the duration of leaf elongation and a concomitant increase in elongation rate, which diminished with increased genotypic dwarfness. Accordingly, temperature elevation resulted in a significant reduction in leaf-length of the light-grown dwarf genotypes and the dark-grown dwarf and semi-dwarf genotypes. It is suggested that this temperature × light × genotype interaction effect is due to environmental dependent upper limits of elongation rate set by the Rht alleles.Abbreviations PAR
Photosynthetic Active Radiation 相似文献
88.
89.
Molinari J. F.; Moore W. R.; Clark J.; Tanaka R.; Butterfield J. H.; Abraham W. M. 《Journal of applied physiology》1995,79(6):1966-1970
90.
Abraham Dalu Gerald M. Cronin Beverly D. Lyn-Cook Harihara M. Mehendale 《Journal of biochemical and molecular toxicology》1995,10(5):259-264
The resiliency of rats during early postnatal development to CCl4 or to an interactive hepatotoxicity of chlordecone (CD) + CCl4 has been shown to be due to an efficient stimulation of tissue repair. The objective of the current study was to investigate if this is due to efficient expression of transforming growth factor-α (TGF-α) and proto-oncogenes. Postnatally developing (20 day old) and adult (60 day old) male Sprague–Dawley rats were challenged with a single low dose of CCl4 (100 μL/kg, ip) or corn oil. Liver samples were collected during a time course (0–96 h) after the administration of CCl4 and used to examine TGF-α and early (c-fos) and late (H-ras and K-ras) proto-oncogenes mRNA expressions. Significant increases in TGF-α, H-ras, and K-ras gene expressions were evident as early as 12 hours after CCl4 and peaked between 24 and 48 hours in an age-dependent manner as detected by slot-blot analysis. Results of the study revealed three- and twofold increases in TGF-α gene expression in 20 and 60 day old rats, respectively, after CCl4. There were 3.5- and 2.5-fold increases in H-ras and 4.4- and 3.4-fold increases in K-ras in 20 and 60 day old rats, respectively. In contrast, a 10-fold increase in c-fos mRNA expression was evident in 20 day old rats 1 hour after CCl4 treatment, returning to the baseline value by 3 hours, whereas in 60 day old rats, this increase was less than twofold. The overall findings of this study indicate that TGF-α and the early and late proto-oncogene mRNA expressions were enhanced in an age- and time-dependent manner in response to a low dose of CCl4. These results further strengthen the view that the remarkable resiliency of rats to hepatotoxicants during early postnatal development is due to substantial increases in stimulation of hepatocellular regeneration and tissue repair mechanisms, leading to regression of liver injury and recovery. © 1996 John Wiley & Sons, Inc. 相似文献