全文获取类型
收费全文 | 106篇 |
免费 | 5篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2016年 | 1篇 |
2015年 | 4篇 |
2014年 | 2篇 |
2013年 | 8篇 |
2012年 | 6篇 |
2011年 | 8篇 |
2010年 | 4篇 |
2009年 | 4篇 |
2008年 | 9篇 |
2007年 | 6篇 |
2006年 | 4篇 |
2005年 | 9篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 3篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 6篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有111条查询结果,搜索用时 328 毫秒
101.
Capuano M Garcia-Herrero CM Tinto N Carluccio C Capobianco V Coto I Cola A Iafusco D Franzese A Zagari A Navas MA Sacchetti L 《PloS one》2012,7(6):e38906
Type 2 Maturity Onset Diabetes of the Young (MODY2) is a monogenic autosomal disease characterized by a primary defect in insulin secretion and hyperglycemia. It results from GCK gene mutations that impair enzyme activity. Between 2006 and 2010, we investigated GCK mutations in 66 diabetic children from southern Italy with suspected MODY2. Denaturing High Performance Liquid Chromatography (DHPLC) and sequence analysis revealed 19 GCK mutations in 28 children, six of which were novel: p.Glu40Asp, p.Val154Leu, p.Arg447Glyfs, p.Lys458_Cys461del, p.Glu395_Arg397del and c.580-2A>T. We evaluated the effect of these 19 mutations using bioinformatic tools such as Polymorphism Phenotyping (Polyphen), Sorting Intolerant From Tolerant (SIFT) and in silico modelling. We also conducted a functional study to evaluate the pathogenic significance of seven mutations that are among the most severe mutations found in our population, and have never been characterized: p.Glu70Asp, p.His137Asp, p.Phe150Tyr, p.Val154Leu, p.Gly162Asp, p.Arg303Trp and p.Arg392Ser. These seven mutations, by altering one or more kinetic parameters, reduced enzyme catalytic activity by >40%. All mutations except p.Glu70Asp displayed thermal-instability, indeed >50% of enzyme activity was lost at 50°C/30 min. Thus, these seven mutations play a pathogenic role in MODY2 insurgence. In conclusion, this report revealed six novel GCK mutations and sheds some light on the structure-function relationship of human GCK mutations and MODY2. 相似文献
102.
Rebekka?K?SchneiderEmail author Susanne?Ziegler Isabelle?Leisten Monica?SV?Ferreira Anne?Schumacher Bj?rn?Rath Dirk?Fahrenkamp Gerhard?Müller-Newen Martina?Crysandt Stefan?Wilop Edgar?Jost Steffen?Koschmieder Ruth?Knüchel Tim?H?Brümmendorf Patrick?Ziegler 《Journal of hematology & oncology》2014,7(1):92
We characterized bone marrow stromal cells (BMSC) from patients with pre-fibrotic myeloproliferative neoplasms (MPN). MPN-BMSC showed decreased capacity to stimulate the proliferation of colony-forming units of normal hematopoietic stem and progenitor cells and displayed increased matrix remodelling (in particular fibronectin deposition) compared to control BMSC. This finding was confirmed in pre-fibrotic MPN bone marrow biopsies in a tissue microarray (n?=?34), which stained positive for fibronectin in the absence of reticulin as a standard myelofibrosis marker. Fibronectin expression correlated significantly with reduced haemoglobin levels in MPN-patients (p?=?0.007; R2?=?0.42). Our data show significant cell-intrinsic alterations in MPN-MSC and suggest that Fibronectin expression might be applicable as a biomarker for the identification of early myelofibrotic transformation in reticulin-negative MPN. 相似文献
103.
Rossi S D'Amico M Capuano A Romano M Petronella P Di Filippo C 《Mediators of inflammation》2006,2006(4):60285
This study investigated the heme oxygenase-1 (HO-1) and the endotoxin-induced uveitis (EIU) in diabetic streptozotocin (STZ)-hyperglycemic rats. STZ-hyperglycemic rats had impaired levels of the enzyme HO-1 within the ciliary bodies if compared with the nondiabetic rats. STZ-hyperglycemic rats also predisposed the eye to produce high levels of both the cytokines IL-1beta and CXCL8. Subsequent EIU further and significantly (P < .01) increased the cytokines production, an effect partly prevented by hemin treatment. Most importantly, hemin, an inducer of heme oxygenase expression and activity, recovered the huge number of infiltrated polymorphonuclear leukocytes PMN within the ciliary bodies associated with STZ-hyperglycemic state and EIU damage. Impairment of the stress-sensitive enzyme HO-1 in STZ-hyperglycemic rats increases and prolongs the inflammatory response to EIU. 相似文献
104.
105.
A plasma increase of liver enzymes has been recently reported in patients receiving heparin therapy. In this study we have evaluated the toxic effect of heparin infusion in the whole rat and in the isolated and perfused rat liver. No variation of plasma enzymes was observed in heparin-treated rats (10 IU per gram body weight, daily for 12 days). The heparin addition in the perfusion medium (5,000 IU in all) has shown no difference in the kinetics of hepatic enzymes release and in the other parameters of liver function. These data do not confirm a liver-toxic effect of heparin in the rat. 相似文献
106.
Mitchell SV Elkind Kristen Coates Wanling Tai Myunghee C Paik Bernadette Boden-Albala Ralph L Sacco 《BMC neurology》2006,6(1):37-6
Background
Inflammation and inflammatory biomarkers play an important role in atherosclerosis and cardiovascular disease. Little information is available, however, on time course of serum markers of inflammation after stroke. 相似文献107.
BACKGROUND AND PURPOSE: Medetomidine is a selective, specific, and potent alpha2-adrenergic receptor agonist that has been utilized successfully as a sedative/analgesic agent in a variety of domestic and nondomestic animals. The objective of this study was to document the physiological effects of the intravenous administration of medetomidine in rhesus macaques (Macaca mulatta). METHODS: Fifteen healthy rhesus macaques (Macaca mulatta), 5 to 15 years old and weighing 5.5 to 11.8 kg, were given four dosages of medetomidine (50, 100, 150, and 200 microg/kg of body weight) intravenously, and cardiovascular, respiratory, thermoregulatory, sedative, and analgesic effects were determined. RESULTS: All four doses of medetomidine induced a similar and significant decrease in mean arterial pressure, as well as a transient but significant increase in respiratory rate followed by a longer-lasting significant decrease. Bradycardia, hypotension, and loss of thermoregulatory ability accompanied by a biphasic respiratory response and inconsistent sedation, analgesia, and muscular relaxation were observed. Heart rate decrease was rapid for all doses, but was significantly lower and of shorter duration after administration of the 50 microg/kg dosage. CONCLUSION: The inconsistency of the anesthetic plane induced by intravenous administration of medetomidine precludes it from being used alone to sedate rhesus macaques. 相似文献
108.
109.
110.
Roberta Miglio Stefano Palmery Mario Salvalaggio Lino Carnelli Federico Capuano Raffaella Borrelli 《Journal of applied phycology》2013,25(6):1621-1631
The present study aims to develop a methodology via Fourier transform infrared (FT-IR) spectroscopy for the semiquantitative determination of triacylglycerols (TAGs) in microalgal consortia, consistent with the use of the technique as process control. FT-IR spectroscopy has proved to be a powerful analytical tool for the identification of macromolecular pools (e.g., proteins, lipids, and carbohydrates) and in monitoring biochemical changes (including lipids) in response to nutrient stress or environmental modifications. In the Oocystis-based consortium under examination, the synthesis of neutral lipid in the form of TAGs can be induced, applying stress condition, and these lipids are suitable as biodiesel precursors. In the exponential growing phase, the consortium shows a low TAGs content, in the order of 5 %w, that can be increased till around 22 %w on ash free dry matter, after nitrogen starvation. 相似文献