全文获取类型
收费全文 | 745篇 |
免费 | 104篇 |
国内免费 | 1篇 |
出版年
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 16篇 |
2014年 | 13篇 |
2013年 | 17篇 |
2012年 | 21篇 |
2011年 | 18篇 |
2010年 | 23篇 |
2009年 | 10篇 |
2008年 | 19篇 |
2007年 | 22篇 |
2006年 | 25篇 |
2005年 | 27篇 |
2004年 | 32篇 |
2003年 | 16篇 |
2002年 | 32篇 |
2001年 | 27篇 |
2000年 | 24篇 |
1999年 | 32篇 |
1998年 | 16篇 |
1997年 | 15篇 |
1996年 | 9篇 |
1995年 | 5篇 |
1994年 | 12篇 |
1993年 | 14篇 |
1992年 | 28篇 |
1991年 | 23篇 |
1990年 | 12篇 |
1989年 | 16篇 |
1988年 | 24篇 |
1987年 | 30篇 |
1986年 | 25篇 |
1985年 | 26篇 |
1984年 | 10篇 |
1983年 | 21篇 |
1982年 | 10篇 |
1981年 | 6篇 |
1980年 | 11篇 |
1979年 | 14篇 |
1978年 | 19篇 |
1977年 | 12篇 |
1976年 | 8篇 |
1975年 | 11篇 |
1974年 | 13篇 |
1973年 | 8篇 |
1971年 | 6篇 |
1970年 | 10篇 |
1969年 | 4篇 |
1967年 | 5篇 |
1966年 | 5篇 |
排序方式: 共有850条查询结果,搜索用时 31 毫秒
101.
Xing GW Wu D Poles MA Horowitz A Tsuji M Ho DD Wong CH 《Bioorganic & medicinal chemistry》2005,13(8):2907-2916
Two novel hybrid molecules 3-O-sulfo-alpha/beta-galactosylceramide 3 and 4, which are derived from an immunostimulatory agent alpha-GalCer 1 and self-glycolipid ligand sulfatide 2, were designed and synthesized. Compound 3 was shown to efficiently stimulate human NKT cells to secret IL-4 and IFN-gamma, with activities similar to 1, suggesting that modification of the 3'-OH position of the galactose moiety with sulfate has no significant effect on NKT cell stimulation. As a comparison, the beta-isomer 4 has no affinity to NKT cells, which demonstrates that the alpha-glycosidic bond of galactosylceramide is crucial to the NKT cells activation. 相似文献
102.
Brown AM 《Genome biology》2005,6(9):231-5
The canonical Wnt signaling pathway is highly conserved in evolution, widely used throughout animal development, and frequently hyperactive in cancer. Although Wnt signaling has been the subject of extensive genetic analysis in the past, some 200 genes have now been identified as candidate modulators of this pathway by a recent study using high-throughput RNAi screening. 相似文献
103.
Cristiana Vitale Giuseppe Mercuro Carlotta Castiglioni Alessandra Cornoldi Arianna Tulli Massimo Fini Maurizio Volterrani Giuseppe MC Rosano 《Cardiovascular diabetology》2005,4(1):1-8
Background
Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARγ) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome.Methods
In a double-blind, parallel-group, randomized study, patients with World Health Organization criteria for metabolic syndrome received once-daily doses of telmisartan (80 mg, n = 20) or losartan (50 mg, n = 20) for 3 months. At baseline and end of treatment, fasting and postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA1c) and 24-hour mean systolic and diastolic blood pressures were determined.Results
Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin resistance and HbAic. Following treatment, plasma glucose and insulin were reduced during the oral glucose tolerance test by telmisartan, but not by losartan. Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with losartan.Conclusion
As well as providing superior 24-hour blood pressure control, telmisartan, unlike losartan, displayed insulin-sensitizing activity, which may be explained by its partial PPARγ activity. 相似文献104.
Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current 总被引:5,自引:0,他引:5
下载免费PDF全文
![点击此处可从《The Journal of general physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Horowitz LF Hirdes W Suh BC Hilgemann DW Mackie K Hille B 《The Journal of general physiology》2005,126(3):243-262
We have further tested the hypothesis that receptor-mediated modulation of KCNQ channels involves depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide-specific phospholipase C (PLC). We used four parallel assays to characterize the agonist-induced PLC response of cells (tsA or CHO cells) expressing M1 muscarinic receptors: translocation of two fluorescent probes for membrane lipids, release of calcium from intracellular stores, and chemical measurement of acidic lipids. Occupation of M1 receptors activates PLC and consumes cellular PIP2 in less than a minute and also partially depletes mono- and unphosphorylated phosphoinositides. KCNQ current is simultaneously suppressed. Two inhibitors of PLC, U73122 and edelfosine (ET-18-OCH3), can block the muscarinic actions completely, including suppression of KCNQ current. However, U73122 also had many side effects that were attributable to alkylation of various proteins. These were mimicked or occluded by prior reaction with the alkylating agent N-ethylmaleimide and included block of pertussis toxin-sensitive G proteins and effects that resembled a weak activation of PLC or an inhibition of lipid kinases. By our functional criteria, the putative PLC activator m-3M3FBS did stimulate PLC, but with a delay and an irregular time course. It also suppressed KCNQ current. The M1 receptor-mediated activation of PLC and suppression of KCNQ current were stopped by lowering intracellular calcium well below resting levels and were slowed by not allowing intracellular calcium to rise in response to PLC activation. Thus calcium release induced by PLC activation feeds back immediately on PLC, accelerating it during muscarinic stimulation in strong positive feedback. These experiments clarify important properties of receptor-coupled PLC responses and their inhibition in the context of the living cell. In each test, the suppression of KCNQ current closely paralleled the expected fall of PIP2. The results are described by a kinetic model. 相似文献
105.
Horowitz JC Lee DY Waghray M Keshamouni VG Thomas PE Zhang H Cui Z Thannickal VJ 《The Journal of biological chemistry》2004,279(2):1359-1367
Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine involved in differentiation, growth, and survival of mesenchymal cells while inhibiting growth/survival of most other cell types. The mechanism(s) of pro-survival signaling by TGF-beta1 in mesenchymal cells is unclear. In this report, we demonstrate that TGF-beta1 protects against serum deprivation-induced apoptosis of mesenchymal cells isolated from patients with acute lung injury and of normal human fetal lung fibroblasts (IMR-90). TGF-beta receptor(s)-activated signaling in these cells involves rapid activation of the Smad and p38 MAPK pathways within minutes of TGF-beta1 treatment followed by a more delayed activation of the pro-survival phosphatidylinositol 3-kinase-protein kinase B (PKB)/Akt pathway. Pharmacological inhibition of p38 MAPK with SB203580 or expression of a p38 kinase-deficient mutant protein inhibits TGF-beta1-induced PKB/Akt phosphorylation. Conditioned medium from TGF-beta1-treated cells rapidly induces PKB/Akt activation in an SB203580- and suramin-sensitive manner, suggesting p38 MAPK-dependent production of a secreted growth factor that activates this pro-survival pathway by an autocrine/paracrine mechanism. Inhibition of the phosphatidylinositol 3-kinase-PKB/Akt pathway blocks TGF-beta1-induced resistance to apoptosis. These results demonstrate the activation of a novel TGF-beta1-activated pro-survival/anti-apoptotic signaling pathway in mesenchymal cells/fibroblasts that may explain cell-specific actions of TGF-beta1 and provide mechanistic insights into its pro-fibrotic and tumor-promoting effects. 相似文献
106.
107.
Effect of fatty acid chain length on suppression of ghrelin and stimulation of PYY, GLP-2 and PP secretion in healthy men 总被引:2,自引:0,他引:2
Feltrin KL Patterson M Ghatei MA Bloom SR Meyer JH Horowitz M Feinle-Bisset C 《Peptides》2006,27(7):1638-1643
We have evaluated the effects of fatty acid chain length on ghrelin, peptide YY (PYY), glucagon-like peptide-2 (GLP-2) and pancreatic polypeptide (PP) secretion and hypothesized that intraduodenal administration of dodecanoic ("C12"), but not decanoic ("C10"), acid would decrease plasma ghrelin and increase PYY, GLP-2 and PP concentrations. Plasma hormone concentrations were measured in seven healthy men during 90-min intraduodenal infusions of: (i) C12, (ii) C10 or (iii) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10) and after a buffet-meal consumed following the infusion. C12 markedly suppressed plasma ghrelin and increased both PYY and GLP-2 (all P < 0.05) compared with control and C10, while C10 had no effect. Both C10 and C12 increased PP concentrations slightly (P < 0.05). We conclude that the effects of intraduodenal fatty acids on ghrelin, PYY and GLP-2 secretion are dependent on their chain length. 相似文献
108.
Pilichiewicz AN Little TJ Brennan IM Meyer JH Wishart JM Otto B Horowitz M Feinle-Bisset C 《American journal of physiology. Regulatory, integrative and comparative physiology》2006,290(3):R668-R677
Enterally administered lipid modulates antropyloroduodenal motility, gut hormone release, appetite, and energy intake. We hypothesized that these effects would be dependent on both the load, and duration, of small intestinal exposure to lipid. Eleven healthy men were studied on four occasions in a double-blind, randomized, fashion. Antropyloroduodenal motility, plasma CCK and peptide YY (PYY) concentrations, and appetite perceptions were measured during intraduodenal infusion of lipid (Intralipid) at 1) 1.33 kcal/min for 50 min, 2) 4 kcal/min for 50 min, and 3) 1.33 kcal/min for 150 min, or 4) saline for 150 min. Immediately after the infusions, energy intake was quantified. Pressure wave sequences (PWSs) were suppressed, and basal pyloric pressure, isolated pyloric pressure waves (IPPWs), plasma CCK and PYY stimulated (all P < 0.05), during the first 50 min of lipid infusion, in a load-dependent fashion. The effect of the 4 kcal/min infusion was sustained so that the suppression of antral pressure waves (PWs) and PWSs and increase in PYY remained evident after cessation of the infusion (all P < 0.05). The prolonged lipid infusion (1.33 kcal/min for 150 min) suppressed antral PWs, stimulated CCK and PYY and basal pyloric pressure (all P < 0.05), and tended to stimulate IPPWs when compared with saline throughout the entire infusion period. There was no significant effect of any of the lipid infusions on appetite or energy intake, although nausea was slightly higher (P < 0.05) with the 4 kcal/min infusion. In conclusion, both the load, and duration, of small intestinal lipid influence antropyloroduodenal motility and patterns of CCK and PYY release. 相似文献
109.
Identification and Localization of a Rickettsia sp. in Bemisia tabaci (Homoptera: Aleyrodidae) 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yuval Gottlieb Murad Ghanim Elad Chiel Dan Gerling Vitaly Portnoy Shimon Steinberg Galil Tzuri A. Rami Horowitz Eduard Belausov Neta Mozes-Daube Svetlana Kontsedalov Moshe Gershon Shunit Gal Nurit Katzir Einat Zchori-Fein 《Applied microbiology》2006,72(5):3646-3652
Whiteflies (Homoptera: Aleyrodidae) are sap-sucking insects that harbor “Candidatus Portiera aleyrodidarum,” an obligatory symbiotic bacterium which is housed in a special organ called the bacteriome. These insects are also home for a diverse facultative microbial community which may include Hamiltonella, Arsenophonus, Fritchea, Wolbachia, and Cardinium spp. In this study, the bacteria associated with a B biotype of the sweet potato whitefly Bemisia tabaci were characterized using molecular fingerprinting techniques, and a Rickettsia sp. was detected for the first time in this insect family. Rickettsia sp. distribution, transmission and localization were studied using PCR and fluorescence in situ hybridizations (FISH). Rickettsia was found in all 20 Israeli B. tabaci populations screened but not in all individuals within each population. A FISH analysis of B. tabaci eggs, nymphs, and adults revealed a unique concentration of Rickettsia around the gut and follicle cells, as well as a random distribution in the hemolymph. We postulate that the Rickettsia enters the oocyte together with the bacteriocytes, leaves these symbiont-housing cells when the egg is laid, multiplies and spreads throughout the egg during embryogenesis and, subsequently, disperses throughout the body of the hatching nymph, excluding the bacteriomes. Although the role Rickettsia plays in the biology of the whitefly is currently unknown, the vertical transmission on the one hand and the partial within-population infection on the other suggest a phenotype that is advantageous under certain conditions but may be deleterious enough to prevent fixation under others. 相似文献
110.