全文获取类型
收费全文 | 781篇 |
免费 | 72篇 |
专业分类
853篇 |
出版年
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 10篇 |
2019年 | 6篇 |
2018年 | 10篇 |
2017年 | 10篇 |
2016年 | 22篇 |
2015年 | 32篇 |
2014年 | 47篇 |
2013年 | 55篇 |
2012年 | 73篇 |
2011年 | 54篇 |
2010年 | 37篇 |
2009年 | 33篇 |
2008年 | 38篇 |
2007年 | 50篇 |
2006年 | 36篇 |
2005年 | 44篇 |
2004年 | 54篇 |
2003年 | 54篇 |
2002年 | 26篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 7篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1973年 | 3篇 |
1971年 | 3篇 |
1968年 | 3篇 |
1963年 | 2篇 |
1945年 | 2篇 |
1942年 | 2篇 |
1921年 | 2篇 |
1909年 | 2篇 |
排序方式: 共有853条查询结果,搜索用时 15 毫秒
61.
Descamps F Brouta F Vermout S Monod M Losson B Mignon B 《FEMS immunology and medical microbiology》2003,38(1):29-34
A secreted 31.5-kDa keratinolytic subtilase (SUB3; AJ431180) is thought to be a Microsporum canis virulence factor and represents a candidate for vaccination trials. In this study, the recombinant keratinase (r-SUB3) was produced by the Pichia pastoris expression system and purified to homogeneity. Recombinant SUB3 displayed identical biochemical properties with the native protease. Experimentally cutaneously infected guinea pigs showed specific lymphoproliferative response towards r-SUB3, while no specific humoral immune response was induced except for one animal. The heterologous expression of SUB3 provides a valuable tool for addressing further investigations on the role of this keratinase in the specific cellular immune response and on its use in vaccination trials in the cat. 相似文献
62.
The effects of Mg(2+) concentration on the kinetics of both ATP cleavage and carboxyenzyme formation in the approach to steady state of the biotin carboxylation reaction of pyruvate carboxylase have been studied. It was found that the enzyme underwent dilution inactivation at low Mg(2+) concentrations and that this occurred at higher enzyme concentrations than had been previously observed. At 10 mM Mg(2+), dilution inactivation was prevented and activation of the enzyme also occurred. When the enzyme was mixed with an ATP solution to initiate the carboxylation reaction, dilution inactivation was reversed and further enzyme activation was induced to a final level that was dependent on Mg(2+) concentration. With the exception of the reaction at 10 mM Mg(2+) in the presence of acetyl CoA, the experimental data could be adequately described as first-order exponential approaches to steady state. At 10 mM Mg(2+) in the presence of acetyl CoA, both ATP cleavage and carboxyenzyme formation data were best described as a biexponential process, in which there was little ATP turnover at steady state. Modeling studies have been performed which produced simulated data that were similar to the experimental data, using a reaction scheme modified from one proposed previously [Legge, G. B., et al. (1996) Biochemistry 35, 3849-3856]. These studies indicate that the major foci of action of Mg(2+) are in the decarboxylation of the enzyme-carboxybiotin complex, the return of the biotin to the site of the biotin carboxylation reaction, and the coupling of ATP cleavage to biotin carboxylation. 相似文献
63.
Chondrocyte extracellular matrix synthesis and turnover are influenced by static compression in a new alginate disk culture system 总被引:7,自引:0,他引:7
Ragan PM Chin VI Hung HH Masuda K Thonar EJ Arner EC Grodzinsky AJ Sandy JD 《Archives of biochemistry and biophysics》2000,383(2):256-264
The goal of this study was to examine the effects of mechanical compression on chondrocyte biosynthesis of extracellular matrix (ECM) components during culture in a new alginate disk culture system. Specifically, we have examined chondrocyte biosynthesis rates, and the structure of aggrecan core protein species present in the cell-associated matrix (CM), in the further removed matrix (FRM) and in the surrounding culture medium. In this alginate disk culture system, chondrocytes can be subjected to mechanical deformations similar to those experienced in vivo. Our results show that over an 8-week culture period, chondrocytes synthesize a functional ECM and can respond to mechanical forces similarly to chondrocytes maintained in native cartilage. In the alginate disk system, static compression was shown to decrease and dynamic compression to increase synthesis of aggrecan of bovine chondrocytes. Western blot analysis of the core proteins of aggrecan molecules identified a number of different species that were present in different relative amounts in the CM, FRM, and medium. Over 21 days of culture, the predominant form of aggrecan found in the ECM was a full-length link-stabilized species. In addition, our data show that the application of 40 h of static compression caused an increase in the proportion of newly synthesized aggrecan molecules released into the medium. However, this was not accompanied by a significant change in the size and composition of aggrecan and aggrecan fragments in the different compartments, suggesting that mechanical compression did not alter the catabolic pathways. Together, these data show that chondrocyte function is maintained in an alginate disk culture system and that this culture system is a useful model to examine chondrocyte ECM assembly and some aspects of catabolism normally found in vivo. 相似文献
64.
Sandy Weidlich Sonja Müller Klaus H. Hoffmann Joseph Woodring 《Archives of insect biochemistry and physiology》2013,83(2):69-85
The secretion of amylase and cellulase in Gryllus bimaculatus is determined by increased food intake, whereby shortly after molting food consumption increases. About half of the standing amylase concentration (activity) in the endothelial cells can be secreted within 30 min. The peak of amylase and cellulase secretion that occurs in the photophase is related to the feeding peak in the previous scotophase. The secretion of chitinase on the other hand is primarily controlled by the molting cycle. Only amylase secretion was affected by calcium in the incubation medium, suggesting an apocrine release mechanism. Refeeding experiments (after 5 days without food) suggest that the release of amylase in response to a nutrient in the lumen (glucose) is not due to simple stimulation of exocytosis, but rather a stimulation of synthesis. 相似文献
65.
Sandy Weidlich Klaus H. Hoffmann Joseph Woodring 《Archives of insect biochemistry and physiology》2015,90(4):209-217
Little is known concerning the sites and the ratios of the lipase secretions in insects, therefore we undertook an examination of the lipase secretion of fed and unfed adult female Gryllus bimaculatus. The ratio of triacylglyceride lipase, diacylglyceride lipase, and phosphatidylcholine lipase secreted by fed females in the caecum and ventriculus is 1:1.4:0.4. These activities decrease in the caecum by 30–40% in unfed females. The total lipase activity (TLA) in the caecum is about 10 times that in the ventriculus. Minimal lipase secretion occurs before and during the final moult, and remains at this level in unfed crickets, indicating a basal secretion rate. In 2‐day‐old fed females, about 10% of the TLA in the entire gut is found in the crop, about 70% in the caecum, 20% in the ventriculus, and 3% in the ileum. Lipases in the ventriculus are recycled back to the caecum and little is lost in the feces. Oleic acid stimulated in vitro lipase secretion, but lipids did not. Feeding stimulated lipase secretion, starvation reduced lipase secretion, but this does not prove a direct prandal regulation of secretion, because feeding also induced a size and volume increase of the caecum. 相似文献
66.
Giron-Michel J Azzi S Khawam K Mortier E Caignard A Devocelle A Ferrini S Croce M François H Lecru L Charpentier B Chouaib S Azzarone B Eid P 《PloS one》2012,7(2):e31624
The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5), by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation). 相似文献
67.
Saskia Lüde Michael T?r?k Sandy Dieterle René J?ggi Karin Berger Büter Stephan Kr?henbühl 《Phytomedicine》2008,15(1-2):120-131
Kava extracts are used widely for different purposes and were thought to be safe. Recently, several cases of hepatotoxicity have been published. To explore possible mechanisms of kava hepatotoxicity, we prepared and analyzed three different kava extracts (a methanolic and an acetonic root and a methanolic leaf extract), and investigated their toxicity on HepG2 cells and isolated rat liver mitochondria. All three extracts showed cytotoxicity starting at a concentration of 50 microg/ml (lactate dehydrogenase leakage) or 1 microg/ml (MTT test). The mitochondrial membrane potential was decreased (root extracts starting at 50 microg/ml) and the respiratory chain inhibited and uncoupled (root extracts) or only uncoupled (leaf extract) at 150 microg/ml, and mitochondrial beta-oxidation was inhibited by all extracts starting at 100 microg/ml. The ratio oxidized to reduced glutathione was increased in HepG2 cells, whereas the cellular ATP content was maintained. Induction of apoptosis was demonstrated by all extracts at a concentration of 150 microg/ml. These results indicate that the kava extracts are toxic to mitochondria, leading to inhibition of the respiratory chain, increased ROS production, a decrease in the mitochondrial membrane potential and eventually to apoptosis of exposed cells. In predisposed patients, mitochondrial toxicity of kava extract may explain hepatic adverse reactions of this drug. 相似文献
68.
Vallabh O. Shah Casey Carroll Ryan Mals Donica Ghahate Jeanette Bobelu Phillip Sandy Kathleen Colleran Ronald Schrader Thomas Faber Mark R. Burge 《PloS one》2015,10(5)
Introduction
One in three people will be diagnosed with diabetes by 2050, and the proportion will likely be higher among Native Americans. Diabetes control is currently suboptimal in underserved populations despite a plethora of new therapies. Patient empowerment is a key determinant of diabetes control, but such empowerment can be difficult to achieve due to resource limitation and cultural, language and health literacy barriers. We describe a home-based educational intervention using Community Health Representatives (CHRs), leading to improvement in Patient Activation Measures scores and clinical indicators of diabetes control.Methods
Sixty participants with type 2 diabetes (T2D) completed a baseline evaluation including physical exam, Point of Care (POC) testing, and the Patient Activation Measure (PAM) survey. Participants then underwent a one hour group didactic session led by Community Health Representatives (CHRs) who subsequently carried out monthly home-based educational interventions to encourage healthy lifestyles, including diet, exercise, and alcohol and cigarette avoidance until follow up at 6 months, when clinical phenotyping and the PAM survey were repeated.Results
PAM scores were increased by at least one level in 35 (58%) participants, while 24 participants who started at higher baseline score did not change. Six months after intervention, mean levels of A1C decreased by 0.7 ± 1.2%; fasting blood glucose decreased by 24.0 ± 38.0 mg/dl; BMI decreased by 1.5 ± 2.1 kg/m2; total cholesterol decreased by 12.0± 28.0 mg/dl; and triglycerides decreased by 52.0 ± 71.0 mg/dl. All of these changes were statistically significant (p<0.05).Conclusion
This six month, CHR led and community-oriented educational intervention helps inform standards of practice for the management of diabetes, engages diabetic populations in their own care, and reduces health disparities for the underserved population of Zuni Indians.Trial Registration
ClinicalTrials.gov NCT02339311 相似文献69.
Elie A. Akl Fadi El-Jardali Lama Bou Karroum Jamale El-Eid Hneine Brax Chaza Akik Mona Osman Ghayda Hassan Mira Itani Aida Farha Kevin Pottie Sandy Oliver 《PloS one》2015,10(9)