全文获取类型
收费全文 | 139篇 |
免费 | 13篇 |
出版年
2023年 | 2篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2018年 | 1篇 |
2016年 | 5篇 |
2015年 | 2篇 |
2014年 | 11篇 |
2013年 | 11篇 |
2012年 | 11篇 |
2011年 | 7篇 |
2010年 | 8篇 |
2009年 | 8篇 |
2008年 | 13篇 |
2007年 | 11篇 |
2006年 | 8篇 |
2005年 | 5篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
排序方式: 共有152条查询结果,搜索用时 15 毫秒
11.
Three-dimensional reconstruction of tarantula myosin filaments suggests how phosphorylation may regulate myosin activity 总被引:1,自引:0,他引:1
Alamo L Wriggers W Pinto A Bártoli F Salazar L Zhao FQ Craig R Padrón R 《Journal of molecular biology》2008,384(4):780-797
Muscle contraction involves the interaction of the myosin heads of the thick filaments with actin subunits of the thin filaments. Relaxation occurs when this interaction is blocked by molecular switches on these filaments. In many muscles, myosin-linked regulation involves phosphorylation of the myosin regulatory light chains (RLCs). Electron microscopy of vertebrate smooth muscle myosin molecules (regulated by phosphorylation) has provided insight into the relaxed structure, revealing that myosin is switched off by intramolecular interactions between its two heads, the free head and the blocked head. Three-dimensional reconstruction of frozen-hydrated specimens revealed that this asymmetric head interaction is also present in native thick filaments of tarantula striated muscle. Our goal in this study was to elucidate the structural features of the tarantula filament involved in phosphorylation-based regulation. A new reconstruction revealed intra- and intermolecular myosin interactions in addition to those seen previously. To help interpret the interactions, we sequenced the tarantula RLC and fitted an atomic model of the myosin head that included the predicted RLC atomic structure and an S2 (subfragment 2) crystal structure to the reconstruction. The fitting suggests one intramolecular interaction, between the cardiomyopathy loop of the free head and its own S2, and two intermolecular interactions, between the cardiac loop of the free head and the essential light chain of the blocked head and between the Leu305-Gln327 interaction loop of the free head and the N-terminal fragment of the RLC of the blocked head. These interactions, added to those previously described, would help switch off the thick filament. Molecular dynamics simulations suggest how phosphorylation could increase the helical content of the RLC N-terminus, weakening these interactions, thus releasing both heads and activating the thick filament. 相似文献
12.
Expression of nonstructural rotavirus protein NSP4 mimics Ca2+ homeostasis changes induced by rotavirus infection in cultured cells 下载免费PDF全文
Díaz Y Chemello ME Peña F Aristimuño OC Zambrano JL Rojas H Bartoli F Salazar L Chwetzoff S Sapin C Trugnan G Michelangeli F Ruiz MC 《Journal of virology》2008,82(22):11331-11343
Rotavirus infection modifies Ca2+ homeostasis, provoking an increase in Ca2+ permeation, the cytoplasmic Ca2+ concentration ([Ca2+]cyto), and total Ca2+ pools and a decrease in Ca2+ response to agonists. A glycosylated viral protein(s), NSP4 and/or VP7, may be responsible for these effects. HT29 or Cos-7 cells were infected by the SA11 clone 28 strain, in which VP7 is not glycosylated, or transiently transfected with plasmids coding for NSP4-enhanced green fluorescent protein (EGFP) or NSP4. The permeability of the plasma membrane to Ca2+ and the amount of Ca2+ sequestered in the endoplasmic reticulum released by carbachol or ATP were measured in fura-2-loaded cells at the single-cell level under a fluorescence microscope or in cell suspensions in a fluorimeter. Total cell Ca2+ pools were evaluated as 45Ca2+ uptake. Infection with SA11 clone 28 induced an increase in Ca2+ permeability and 45Ca2+ uptake similar to that found with the normally glycosylated SA11 strain. These effects were inhibited by tunicamycin, indicating that inhibition of glycosylation of a viral protein other than VP7 affects the changes of Ca2+ homeostasis induced by infection. Expression of NSP4-EGFP or NSP4 in transfected cells induced the same changes observed with rotavirus infection, whereas the expression of EGFP or EGFP-VP4 showed the behavior of uninfected and untransfected cells. Increased 45Ca2+ uptake was also observed in cells expressing NSP4-EGFP or NSP4, as evidenced in rotavirus infection. These results indicate that glycosylated NSP4 is primarily responsible for altering the Ca2+ homeostasis of infected cells through an initial increase of cell membrane permeability to Ca2+. 相似文献
13.
Galectin-1 in cartilage: Expression, influence on chondrocyte growth and interaction with ECM components 总被引:1,自引:0,他引:1
Eleonora Marsich Pamela Mozetic Fulvia Ortolani Magali Contin Maurizio Marchini Amedeo Vetere Sabrina Pacor Sabrina Semeraro Franco Vittur Sergio Paoletti 《Matrix biology》2008,27(6):513-525
Galectin-1 is a 14 kDa beta-galactoside binding protein, capable of forming lattice-like structures with glycans of cellular glycoconjugates and inducing intracellular signaling. The expression of Galectin-1 in porcine cartilage is described in this work for the first time. Immunocytochemical methods revealed distinct distribution patterns for both articular and growth plate cartilage. In articular cartilage, the highest reactivity for Galectin-1 was found in all chondrocytes at the superficial zone and in most of those at the lower layer of the middle zone. In the growth plate, marked reactivity was seen in chondrocytes at the proliferative zone and reached a maximum level for the column-forming cells at the hypertrophic zone. In addition, different Galectin-1 distribution patterns were observed at the subcellular level. With regards to the metabolic effects of Galectin-1, the results in vitro seem to indicate an inhibitory effect of Galectin-1 on articular chondrocyte anabolism (i.e. inhibition of cell proliferation and anabolic gene expression) and a stimulation of catabolic processes (i.e. induction of matrix degradation and hypertrophy marker expression). These data represent a starting point for the understanding the molecular mechanisms underlining ECM-Galectin-1 interaction and the subsequent signaling-cell transduction processes involving cartilage formation and maturation. 相似文献
14.
Fulvia Gloria-Bottini Nazzareno Lucarini Ricciotti Palmarino Mauro La Torre A. Amante E. Bottini 《Human genetics》1997,101(2):158-164
We have studied the pattern of association between the season of conception and cytosolic low molecular weight phosphotyrosine
phosphatase (ACP1) genetic polymorphism in 329 consecutively newborn infants from the population of Penne and 361 consecutively
newborn infants from the population of Rome. In addition, 329 mothers were studied in the population of Penne. A concordant,
highly significant association was observed in the two populations between ACP1 parameters and the season of conception of
newborn infants. The total activity of ACP1 shows a minimum in infants conceived in January–February and a maximum in those
conceived at the end of the solar year. Analysis of the joint mother-newborn ACP1 distribution in relation to the season of
fertilisation has shown that among mothers carrying ACP1*A (the allele showing the lowest activity), the proportion of newborns
carrying this allele is higher in those conceived in the first months of the year than in those conceived subsequently. Since
ACP1 probably functions as a phosphotyrosine phosphatase and as a flavin mononucleotide phosphatase, low activity could enhance
the metabolic rate and would be advantageous in a cold environment. The cycle of variation of ACP1 in infants follows the
cycle of solar illumination. It is possible that individuals who have a genetic background allowing them to adapt easily and
readily to seasonal demand are more successful in reproducing themselves. The population of zygotes conceived in a given season
would therefore reproduce the pattern of gene combination more fit for that season.
Received: 15 June 1997 / Accepted: 31 July 1997 相似文献
15.
Are Subject-Specific Musculoskeletal Models Robust to the Uncertainties in Parameter Identification?
Giordano Valente Lorenzo Pitto Debora Testi Ajay Seth Scott L. Delp Rita Stagni Marco Viceconti Fulvia Taddei 《PloS one》2014,9(11)
Subject-specific musculoskeletal modeling can be applied to study musculoskeletal disorders, allowing inclusion of personalized anatomy and properties. Independent of the tools used for model creation, there are unavoidable uncertainties associated with parameter identification, whose effect on model predictions is still not fully understood. The aim of the present study was to analyze the sensitivity of subject-specific model predictions (i.e., joint angles, joint moments, muscle and joint contact forces) during walking to the uncertainties in the identification of body landmark positions, maximum muscle tension and musculotendon geometry. To this aim, we created an MRI-based musculoskeletal model of the lower limbs, defined as a 7-segment, 10-degree-of-freedom articulated linkage, actuated by 84 musculotendon units. We then performed a Monte-Carlo probabilistic analysis perturbing model parameters according to their uncertainty, and solving a typical inverse dynamics and static optimization problem using 500 models that included the different sets of perturbed variable values. Model creation and gait simulations were performed by using freely available software that we developed to standardize the process of model creation, integrate with OpenSim and create probabilistic simulations of movement. The uncertainties in input variables had a moderate effect on model predictions, as muscle and joint contact forces showed maximum standard deviation of 0.3 times body-weight and maximum range of 2.1 times body-weight. In addition, the output variables significantly correlated with few input variables (up to 7 out of 312) across the gait cycle, including the geometry definition of larger muscles and the maximum muscle tension in limited gait portions. Although we found subject-specific models not markedly sensitive to parameter identification, researchers should be aware of the model precision in relation to the intended application. In fact, force predictions could be affected by an uncertainty in the same order of magnitude of its value, although this condition has low probability to occur. 相似文献
16.
17.
Fulvia?RizzaEmail author Ildikó?Karsai Caterina?Morcia Franz-Werner?Badeck Valeria?Terzi Donata?Pagani Tibor?Kiss Antonio?Michele?Stanca 《Molecular breeding : new strategies in plant improvement》2016,36(11):156
Changing climatic conditions with warming winters and shifts in the frequencies of drought, intense rainfall and cold spells together with associated changes in the geographical distribution of arable crops increase the challenges for selecting new varieties. In this context, we aim to contribute to a better understanding of the determinants of barley (Hordeum vulgare) frost tolerance (FRT) and consequent improvements to marker-assisted selection (MAS). Freezing injury in a diversity panel of 121 barley genotypes with different growth habits and origins was assessed using phenotyping based on chlorophyll fluorescence (Fv/Fm) measurements to screen genetic diversity in plants at an early growth stage. The haplotypes of vernalisation and photoperiod genes were determined with PCR, and correlation analyses were done using data from 12 laboratory and field-laboratory FRT tests. Previous results of allelic combinations of VRN-H1/VRN-H2 for FRT were confirmed with these experiments using a larger set of genotypes. The predictive power of polymorphisms in VRN-H1 intron 1 region for FRT was significantly higher than that of the VRN-H1 promoter polymorphism. The vrn-H1/vrn-H2 facultative genotypes had similar or higher FRT than vrn-H1/Vrn-H2 winter genotypes under suboptimal hardening conditions. Genes regulating long-day and short-day photoperiodic responses were significantly correlated with FRT. The most parsimonious model for prediction of FRT was based on polymorphisms in the VRN-H1 intron 1 region, VRN-H2 and PPD-H2 and explained 69% of the variation in FRT. 相似文献
18.
Fulvia Tambone Pierluigi Genevini Giuliana D’ImporzanoFabrizio Adani 《Bioresource technology》2009,100(12):3140-3142
The transformation of organic matter during anaerobic digestion of mixtures of energetic crops, cow slurry, agro-industrial waste and organic fraction of municipal solid waste (OFMSW) was studied by analysing different samples at diverse points during the anaerobic digestion process in a full-scale plant. Both chemical (fiber analysis) and spectroscopic approaches (13C CPMAS NMR) indicated the anaerobic digestion process proceeded by degradation of more labile fraction (e.g. carbohydrate-like molecules) and concentration of more recalcitrant molecules (lignin and non-hydrolysable lipids). These modifications determined a higher degree of biological stability of digestate with respect to the starting mixture, as suggested, also, by the good correlations found between the cumulative oxygen uptake (OD20), and the sum of (cellulose + hemicellulose + cell soluble) contents of biomasses detected by fiber analysis (r = 0.99; P < 0.05), and both O–alkyl-C (r = 0.98; P < 0.05) and alkyl-C (r = −0.99; P < 0.05) measured by 13C CPMAS NMR. 相似文献
19.
Tram Huynh Zhong Chen Suhong Pang Jieping Geng Tiziano Bandiera Simona Bindi Paola Vianello Fulvia Roletto Sandrine Thieffine Arturo Galvani Wayne Vaccaro Michael A. Poss George L. Trainor Matthew V. Lorenzi Marco Gottardis Lata Jayaraman Ashok V. Purandare 《Bioorganic & medicinal chemistry letters》2009,19(11):2924-2927
Design, synthesis, and SAR development led to the identification of the potent, novel, and selective pyrazole based inhibitor (7f) of Coactivator Associated Arginine Methyltransferase (CARM1). 相似文献
20.
Pevarello P Fancelli D Vulpetti A Amici R Villa M Pittalà V Vianello P Cameron A Ciomei M Mercurio C Bischoff JR Roletto F Varasi M Brasca MG 《Bioorganic & medicinal chemistry letters》2006,16(4):1084-1090
We have recently reported about a new class of Aurora-A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. Here we describe the synthesis and early expansion of CDK2/cyclin A-E inhibitors belonging to the same chemical class. Synthesis of the compounds was accomplished using a solution-phase protocol amenable to rapid parallel expansion. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit CDK2-mediated tumor cell proliferation have been obtained. 相似文献