全文获取类型
收费全文 | 316篇 |
免费 | 10篇 |
国内免费 | 2篇 |
专业分类
328篇 |
出版年
2022年 | 4篇 |
2021年 | 9篇 |
2020年 | 4篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 14篇 |
2014年 | 12篇 |
2013年 | 21篇 |
2012年 | 17篇 |
2011年 | 19篇 |
2010年 | 7篇 |
2009年 | 12篇 |
2008年 | 13篇 |
2007年 | 12篇 |
2006年 | 8篇 |
2005年 | 19篇 |
2004年 | 14篇 |
2003年 | 14篇 |
2002年 | 9篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1998年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1968年 | 1篇 |
1965年 | 1篇 |
1964年 | 2篇 |
排序方式: 共有328条查询结果,搜索用时 15 毫秒
21.
22.
Vita Yanti Anggraeni Noriaki Emoto Keiko Yagi Dyah Samti Mayasari Kazuhiko Nakayama Tomomi Izumikawa Hiroshi Kitagawa Ken-ichi Hirata 《Biochemical and biophysical research communications》2011,(1):36
Subendothelial retention of lipoproteins by proteoglycans (PGs) is the initiating event in atherosclerosis. The elongation of chondroitin sulfate (CS) chains is associated with increased low-density lipoprotein (LDL) binding and progression of atherosclerosis. Recently, it has been shown that 2 Golgi enzymes, chondroitin 4-O-sulfotransferase-1 (C4ST-1) and chondroitin N-acetylgalactosaminyltransferase-2 (ChGn-2), play a critical role in CS chain elongation. However, the roles of C4ST-1 and ChGn-2 during the progression of atherosclerosis are not known. The aim of this study was to analyze the expression of C4ST-1 and ChGn-2 in atherosclerotic lesions in vivo and determine whether their expression correlated with CS chain elongation.Low-density lipoprotein receptor knockout (LDLr KO) mice were fed a western diet for 2, 4, and 8 weeks to stimulate development of atherosclerosis. The binding of LDL and CS PG in this mouse model was confirmed by chondroitinase ABC (ChABC) digestion and apolipoprotein B (apo B) staining. Gel filtration analysis revealed that the CS chains began to elongate as early as 2 weeks after beginning a western diet and continued as the atherosclerosis progressed. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) showed that the mRNA levels of C4ST-1 and ChGn-2 increased after 8 weeks of this diet. In contrast, the mRNA levels of their homologs, C4ST-2 and ChGn-1, were unchanged. In addition, immunohistochemical analysis demonstrated that the expression of C4ST-1 and ChGn-2 appeared to have similar site-specific patterns and coincided with biglycan expression at the aortic root.Our results suggested that C4ST-1 and ChGn-2 may be involved in the elongation of CS chains in the arterial wall during the progression of atherosclerosis. Therefore, modulating their expression and activity might be a novel therapeutic strategy for atherosclerosis. 相似文献
23.
A new nonlinear constitutive model for the three-dimensional stress relaxation of articular ligaments is proposed. The model accounts for finite strains, anisotropy, and strain-dependent stress relaxation behavior exhibited by these ligaments. The model parameters are identified using published uniaxial stress–stretch and stress relaxation data on human medial collateral ligaments (MCLs) subjected to tensile tests in the fiber and transverse to the fiber directions (Quapp and Weiss in J Biomech Eng Trans ASME 120:757–763, 1998; Bonifasi-Lista et al. in J Orthop Res 23(1):67–76, 2005). The constitutive equation is then used to predict the nonlinear elastic and stress relaxation response of ligaments subjected to shear deformations in the fiber direction and transverse to the fiber direction, and an equibiaxial extension. A direct comparison with stress relaxation data collected by subjecting human MCLs to shear deformation in the fiber direction is presented in order to demonstrate the predictive capabilities of the model. 相似文献
24.
Toscano A Messina S Campo GM Di Leo R Musumeci O Rodolico C Aguennouz M Annesi G Messina C Vita G 《Free radical research》2005,39(7):771-776
Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy affecting adults. The genetic basis of DM1 consists of a mutational expansion of a repetitive trinucleotide sequence (CTG). The number of triplets expansion divides patients in four categories related to the molecular changes (E1, E2, E3, E4). The pathogenic mechanisms of multi-systemic involvement of DM1 are still unclear. DM1 has been suspected to be due to premature aging, that is known to be sustained by increased free radicals levels and/or decreased antioxidants activities in neurodegenerative disorders. Recently, the gain-of-function at RNA level hypothesis has gained great attention, but oxidative stress might act in the disease progression. We have investigated 36 DM1 patients belonging to 22 unrelated families, 10 patients with other myotonic disorders (OMD) and 22 age-matched healthy controls from the clinical, biochemical and molecular point of view. Biochemical analysis detected blood levels of superoxide dismutase (SOD), malonilaldehyde (MDA), vitamin E (Vit E), hydroxyl radicals (OH) and total antioxidant system (TAS). Results revealed that DM1 patients showed significantly higher levels of SOD (+40%; MAL (+57%; RAD 2 (+106%; and TAS (+20%; than normal controls. Our data support the hypothesis of a pathogenic role of oxidative stress in DM1 and therefore confirm the detrimental role played by free radicals in this pathology and suggest the opportunity to undertake clinical trials with antioxidants in this disorder. 相似文献
25.
A quantitative immunochemical study was carried out of four enzymes, cathodal esterase, acid phosphatase, glucosaminidase and β-glucuronidase. In homogenates of the human diploid cell line WI-38, the relative amounts of the enzymes increased with the passage number of the culture, although great variation was found in later passages just before death of the culture. 相似文献
26.
27.
Messina MF Aguennouz M Arrigo T Rodolico C Valenzise M Musumeci O Vita G Lanzano N De Luca F 《Hormone research》2008,70(2):124-128
Short stature is a well-recognized feature of Duchenne muscular dystrophy, whilst it has been reported rarely in Becker muscular dystrophy (BMD). Here we report two brothers with BMD, who exhibited a very different growth pattern. Whereas in the short brother (-2.2 SDS) molecular investigation revealed a G367A mutation in the short stature homeobox containing (SHOX) gene located in the Xp22.3 region, no abnormality was found in the brother with normal height (-0.1 SDS). Our data suggest that abnormal growth observed in a boy with BMD may be related to an additional genetic alteration, already known as correlated with short stature. 相似文献
28.
Masayuki Hanaoka Mark R Nicolls Andrew P Fontenot Donatas Kraskauskas Douglas G Mack Adelheid Kratzer Jonas Salys Vita Kraskauskiene Nana Burns Norbert F Voelkel Laimute Taraseviciene-Stewart 《Respiratory research》2010,11(1):179
Background
The presence of anti-endothelial cell antibodies and pathogenic T cells may reflect an autoimmune component in the pathogenesis of emphysema. Whether immune modulatory strategies can protect against the development of emphysema is not known.Methods
Sprague Dawley rats were immunized with human umbilical vein endothelial cells (HUVEC) to induce autoimmune emphysema and treated with intrathymic HUVEC-injection and pristane. Measurements of alveolar airspace enlargement, cytokine levels, immuno histochemical, western blot analysis, and T cell repertoire of the lung tissue were performed.Results
The immunomodulatory strategies protected lungs against cell death as demonstrated by reduced numbers of TUNEL and active caspase-3 positive cells and reduced levels of active caspase-3, when compared with lungs from HUVEC-immunized rats. Immunomodulatory strategies also suppressed anti-endothelial antibody production and preserved CNTF, IL-1alpha and VEGF levels. The immune deviation effects of the intrathymic HUVEC-injection were associated with an expansion of CD4+CD25+Foxp3+ regulatory T cells. Pristane treatment decreased the proportion of T cells expressing receptor beta-chain, Vβ16.1 in the lung tissue.Conclusions
Our data demonstrate that interventions classically employed to induce central T cell tolerance (thymic inoculation of antigen) or to activate innate immune responses (pristane treatment) can prevent the development of autoimmune emphysema. 相似文献29.
David Rinaldo Claudio Vita Martin J. Field 《Journal of biomolecular structure & dynamics》2013,31(3):281-297
Abstract Proteins with the ability to specifically bind strontium would potentially be of great use in the field of nuclear waste management. Unfortunately, no such peptides or proteins are known—indeed, it is uncertain whether they exist under natural conditions due to low environmental concentrations of strontium. To investigate the possibility of devising such molecules, one of us (CV), in a previous experimental study [J. Biol. Inorg. Chem. 8, 33440 (2003)], proposed starting from an EF-hand motif of the protein calmodulin and mutating some residues to change the motif's specificity for calcium into one for strontium. In this paper, which represents a theoretical complement to the experimental work, we analyzed small-molecule crystallographic structures and performed quantum chemical calculations to identify possible mutations. We then constructed seven mutant sequences of the EF-hand motif and analyzed their dynamical and binding behaviors using molecular dynamics simulations and free-energy calculations (using the MM/PBSA method). As a result of these analyzes we were able to isolate some characteristics that could lead to mutant peptides with enhanced strontium affinity. 相似文献
30.
Vita Peri Boris Ajdukovic Paul Holland Balwant S. Tuana 《Molecular and cellular biochemistry》1994,130(1):57-65
Dystrophin is a high molecular weight protein present at low abundance in skeletal, cardiac and smooth muscle and in trace amounts in brain. In skeletal muscle, dystrophin is uniformly distributed along the inner surface of the plasma membrane. Biochemical fractionation studies have shown that all detectable skeletal muscle dystrophin is tightly associated with a complex of wheat germ agglutinin (WGA)-binding and concanavalin A (Con A) binding sarcolemmal glycoproteins. Absence of dystrophin is the primary biochemical defect in patients with Duchenne muscular dystrophy and leads to segmental necrosis of their skeletal myofibers. Although present in similar amounts in normal cardiac and skeletal muscle, the absence of dystrophin from cardiac muscle has less severe effects on the survival of cardiac cells. We have therefore examined whether there are differences in the properties of cardiac and skeletal dystrophin. We report that in contrast to skeletal muscle, cardiac dystrophin is distributed between distinct pools: a soluble cytoplasmic pool, a membrane-bound pool not associated with WGA-binding glycoproteins and a membrane-bound pool associated with WGA-binding glycoproteins. Cardiac dystrophin was not associated with any Con A binding glycoproteins. Immunohistochemical localization studies in isolated ventricular myocytes reveal a distinct punctate staining pattern for dystrophin, approximating to the level of the transverse tubule/Z-line and contrasting with the uniform sarcolemmal staining reported for skeletal muscle fibers. The distinct properties of cardiac dystrophin suggest unique roles for this protein in cardiac versus skeletal muscle function.Abbreviations Dys
Dystrophin
- T-tubule
Transverse tubule
- SDS-PAGE
Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis
- WGA
Wheat Germ Agglutinin
- Con A
Concanavalin A
- DHP
Dihydropyridine receptor
- FITC
Fluorescein Isothiocyanate Conjugate
- NAG
N-Acetyl-D-Glucosamine
- NP-40
NONIDET P-40
- PBS
Phosphate-Buffered Saline
- TBST
Tris Buffered Saline-Tween 相似文献