全文获取类型
收费全文 | 107篇 |
免费 | 9篇 |
国内免费 | 4篇 |
出版年
2022年 | 1篇 |
2019年 | 1篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 11篇 |
2013年 | 6篇 |
2012年 | 7篇 |
2011年 | 4篇 |
2010年 | 9篇 |
2009年 | 7篇 |
2008年 | 6篇 |
2007年 | 2篇 |
2006年 | 2篇 |
2005年 | 5篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1983年 | 4篇 |
1978年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有120条查询结果,搜索用时 796 毫秒
111.
RD Calixto R Verlengia AH Crisp TB Carvalho MD Crepaldi AA Pereira AK Yamada GR da Mota CR Lopes 《Biology of sport / Institute of Sport》2014,31(4):289-294
This study aimed to compare the effects of different velocities of eccentric muscle actions on acute blood lactate and serum growth hormone (GH) concentrations following free weight bench press exercises performed by resistance-trained men. Sixteen healthy men were divided into two groups: slow eccentric velocity (SEV; n = 8) and fast eccentric velocity (FEV; n = 8). Both groups performed four sets of eight eccentric repetitions at an intensity of 70% of their one repetition maximum eccentric (1RMecc) test, with 2-minute rest intervals between sets. The eccentric velocity was controlled to 3 seconds per range of motion for SEV and 0.5 seconds for the FEV group. There was a significant difference (P < 0.001) in the kinetics of blood lactate removal (at 3, 6, 9, 15, and 20 min) and higher mean values for peak blood lactate (P = 0.001) for the SEV group (9.1 ± 0.5 mM) compared to the FEV group (6.1 ± 0.4 mM). Additionally, serum GH concentrations were significantly higher (P < 0.001) at 15 minutes after bench press exercise in the SEV group (1.7 ± 0.6 ng · mL−1) relative to the FEV group (0.1 ± 0.0 ng · mL−1). In conclusion, the velocity of eccentric muscle action influences acute responses following bench press exercises performed by resistance-trained men using a slow velocity resulting in a greater metabolic stress and hormone response. 相似文献
112.
Andre M Siqueira Janieldo A Cavalcante Shelia Vítor-Silva Roberto C Reyes-Lecca Aline C Alencar Wuelton M Monteiro Márcia AA Alexandre Mour?o Maria Paula G Caterina Guinovart Quique Bassat Maria das Gra?as C Alecrim Marcus VG Lacerda 《Memórias do Instituto Oswaldo Cruz》2014,109(5):569-576
Anaemia is amongst the major complications of malaria, a major public health problem
in the Amazon Region in Latin America. We examined the haemoglobin (Hb)
concentrations of malaria-infected patients and compared it to that of
malaria-negative febrile patients and afebrile controls. The haematological
parameters of febrile patients who had a thick-blood-smear performed at an infectious
diseases reference centre of the Brazilian Amazon between December 2009-January 2012
were retrieved together with clinical data. An afebrile community control group was
composed from a survey performed in a malaria-endemic area. Hb concentrations and
anaemia prevalence were analysed according to clinical-epidemiological status and
demographic characteristics. In total, 7,831 observations were included. Patients
with Plasmodium falciparum infection had lower mean Hb
concentrations (10.5 g/dL) followed by P. vivax-infected individuals
(12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients
(13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were
strong independent predictors for both outcomes. Amongst malaria-infected
individuals, women in the reproductive age had considerably lower Hb concentrations.
In this moderate transmission intensity setting, both vivax and falciparum malaria
are associated with reduced Hb concentrations and risk of anaemia throughout a wide
age range. 相似文献
113.
Sajin Bae Cornelia M Ulrich Lynn B Bailey Olga Malysheva Elissa C Brown David R Maneval Marian L Neuhouser Ting-Yuan David Cheng Joshua W Miller Yingye Zheng Liren Xiao Lifang Hou Xiaoling Song Katharina Buck Shirley AA Beresford Marie A Caudill 《Epigenetics》2014,9(3):396-403
DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified by one-carbon nutrients. The objective of this study was to investigate the impact of folic acid (FA) fortification of the US food supply on leukocyte global DNA methylation and the relationship between DNA methylation, red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal women enrolled in the Women's Health Initiative Observational Study. We selected 408 women from the highest and lowest tertiles of RBC folate distribution matching on age and timing of the baseline blood draw, which spanned the pre- (1994–1995), peri- (1996–1997), or post-fortification (1998) periods. Global DNA methylation was assessed by liquid chromatography-tandem mass spectrometry and expressed as a percentage of total cytosine. We observed an interaction (P = 0.02) between fortification period and RBC folate in relation to DNA methylation. Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12 vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%; P = 0.03) DNA methylation in the post-fortification period. We also observed significant correlations between one-carbon biomarkers and DNA methylation in the pre-fortification period, but not in the peri- or post-fortification period. The correlation between plasma homocysteine and DNA methylation was reversed from an inverse relationship during the pre-fortification period to a positive relationship during the post-fortification period. Our data suggest that (1) during FA fortification, higher RBC folate status is associated with a reduction in leukocyte global DNA methylation among postmenopausal women and; (2) the relationship between one-carbon biomarkers and global DNA methylation is dependent on folate availability. 相似文献
114.
Martin M. Edreira Sheng Li Daniel Hochbaum Sergio Wong Alemayehu A. Gorfe Fernando Ribeiro-Neto Virgil L. Woods Jr. Daniel L. Altschuler 《The Journal of biological chemistry》2009,284(40):27480-27486
Rap1b has been implicated in the transduction of the cAMP mitogenic response. Agonists that increase intracellular cAMP rapidly activate (i.e. GTP binding) and phosphorylate Rap1b on Ser179 at its C terminus. cAMP-dependent protein kinase (PKA)-mediated phosphorylation of Rap1b is required for cAMP-dependent mitogenesis, tumorigenesis, and inhibition of AKT activity. However, the role of phosphorylation still remains unknown. In this study, we utilized amide hydrogen/deuterium exchange mass spectroscopy (DXMS) to assess potential conformational changes and/or mobility induced by phosphorylation. We report here DXMS data comparing exchange rates for PKA-phosphorylated (Rap1-P) and S179D phosphomimetic (Rap1-D) Rap1b proteins. Rap1-P and Rap1-D behaved exactly the same, revealing an increased exchange rate in discrete regions along the protein; these regions include a domain around the phosphorylation site and unexpectedly the two switch loops. Thus, local effects induced by Ser179 phosphorylation communicate allosterically with distal domains involved in effector interaction. These results provide a mechanistic explanation for the differential effects of Rap1 phosphorylation by PKA on effector protein interaction.Rap1b, a member of the Ras superfamily of small G proteins, is a GTPase that acts as a molecular on/off switch for the transduction of several external stimuli by alternating from an inactive GDP-bound to an active GTP-bound state (1, 2). Rap1 activation is mediated by several second messengers, growth factors, cytokines, and cell adhesion molecules. The steady-state level of Rap1-GTP is tightly regulated by a family of guanine nucleotide exchange factors that catalyze the otherwise slow dissociation of GDP (i.e. activation) and GTPase-activating proteins, which stimulate the rather slow intrinsic GTPase catalytic activity (i.e. inactivation) (3). GTP binding is coupled to conformational changes in two well defined regions, the switch I (residues 30–40) and switch II (residues 60–76) domains, responsible for high affinity interaction with effector molecules (4, 5) and thus downstream signal transduction.cAMP is one among several pathways leading to Rap1 activation (6). cAMP exerts both mitogenic and anti-mitogenic responses in different cell types, and Rap1 activation is required downstream of cAMP in both scenarios (7, 8). Elevation of intracellular cAMP levels activates cAMP-dependent protein kinase (PKA)4 and Epac (exchange protein activated by cAMP), a Rap guanine nucleotide exchange factor (9). Expression of Rap1b in cells where cAMP is mitogenic is associated with an increase in cAMP-mediated G1/S phase entry (7, 10), and both biochemical events, Rap activation and phosphorylation at Ser179, are synergistically required for this action (11).PKA substrates able to modulate Rap1 activity (i.e. Src/C3G recruitment and GTPase-activating protein) were recently reported (12, 13). However, the role of PKA-dependent Rap1 phosphorylation at Ser179 is still unknown. Rap1 phosphorylation does not affect its overall intracellular localization, its basal GTP/GDP exchange reaction, its intrinsic rate of GTP hydrolysis, or its ability to be stimulated by a cytosolic Rap GTPase-activating protein (10); however, several reports suggest that Rap1 phosphorylation is able to modulate its association with some binding partners, namely cytochrome b558 (14) and Raf1 (15). The mechanism by which a modification of Ser179 at the C-terminal end of the molecule affects the regions involved with effector interaction at its N terminus is for the moment unclear.In this study, we report a global assessment of the effects of Ser179 phosphorylation on conformational change/mobility analyzed by hydrogen/deuterium exchange mass spectrometry (DXMS). The results are consistent with an allosteric effect of the C terminus (containing Ser179) to the switch loops/effector domain. 相似文献
115.
Sarfraz A Tunio Neil J Oldfield Dlawer AA Ala'Aldeen Karl G Wooldridge David PJ Turner 《BMC microbiology》2010,10(1):280
Background
Glyceraldehyde 3-phosphate dehydrogenases (GAPDHs) are cytoplasmic glycolytic enzymes, which although lacking identifiable secretion signals, have also been found localized to the surface of several bacteria (and some eukaryotic organisms); where in some cases they have been shown to contribute to the colonization and invasion of host tissues. Neisseria meningitidis is an obligate human nasopharyngeal commensal which can cause life-threatening infections including septicaemia and meningitis. N. meningitidis has two genes, gapA-1 and gapA-2, encoding GAPDH enzymes. GapA-1 has previously been shown to be up-regulated on bacterial contact with host epithelial cells and is accessible to antibodies on the surface of capsule-permeabilized meningococcal cells. The aims of this study were: 1) to determine whether GapA-1 was expressed across different strains of N. meningitidis; 2) to determine whether GapA-1 surface accessibility to antibodies was dependant on the presence of capsule; 3) to determine whether GapA-1 can influence the interaction of meningococci and host cells, particularly in the key stages of adhesion and invasion. 相似文献116.
Albert Eduardo Silva Martins Norma Lucena-Silva Renan Gomes Garcia Stefan Welkovic Aureliana Barboza Maria Luiza Bezerra Menezes Magda Maruza Terezinha Tenório Ricardo AA Ximenes 《Memórias do Instituto Oswaldo Cruz》2014,109(6):738-747
Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of
coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the
presence of the virus favours intraepithelial squamous cell lesion progression and
may induce cancer. The aim of this study was to evaluate the prevalence of HPV
infection, distribution of HPV types and risk factors among HIV-positive patients.
Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic
cytology, colposcopy and HPV presence and type by means of polymerase chain reaction
and sequencing. The results were analysed by comparing demographic data and data
relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the
HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate
analysis showed an association between HPV infection and the presence of cytological
alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of
partners greater than three (p = 0.002), CD4+ lymphocyte count <
200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk
HPV was present in the majority of the lesions studied, the low frequency of HPV 16
(3.3%), low occurrence of cervical lesions and preserved immunological state in most
of the HIV-positive patients were factors that may explain the low occurrence of
precancerous cervical lesions in this population. 相似文献
117.
Dynamic clusters of lipid-anchored Ras proteins are important for high-fidelity signal transduction in cells. The average size of Ras nanoclusters was reported to be independent of protein expression levels, and cholesterol depletion is commonly used to test the raft-preference of nanoclusters. However, whether protein concentration and membrane domain stability affect Ras clustering in a reversible manner is not well understood. We used coarse-grained molecular dynamics simulations to examine the reversibility of the effects of peptide and cholesterol concentrations as well as a lipid domain-perturbing nanoparticle (C60) on the dynamics and stability of H-Ras lipid-anchor nanoclusters. By comparing results from these simulations with previous observations from the literature, we show that effects of peptide/cholesterol concentrations on the dynamics and stability of H-Ras peptide nanoclusters are reversible. Our results also suggest a correlation between the stabilities of lipid domains and Ras nanoclusters, which is supported by our finding that C60 penetrates into the liquid-disordered domain of the bilayer, destabilizing lipid domains and thereby the stability of the nanoclusters. 相似文献
118.
Archives of Microbiology - 相似文献
119.
120.