全文获取类型
收费全文 | 640篇 |
免费 | 71篇 |
国内免费 | 1篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 11篇 |
2019年 | 9篇 |
2018年 | 15篇 |
2017年 | 17篇 |
2016年 | 16篇 |
2015年 | 22篇 |
2014年 | 24篇 |
2013年 | 35篇 |
2012年 | 43篇 |
2011年 | 41篇 |
2010年 | 30篇 |
2009年 | 18篇 |
2008年 | 28篇 |
2007年 | 25篇 |
2006年 | 24篇 |
2005年 | 27篇 |
2004年 | 36篇 |
2003年 | 17篇 |
2002年 | 32篇 |
2001年 | 21篇 |
2000年 | 17篇 |
1999年 | 18篇 |
1998年 | 17篇 |
1997年 | 13篇 |
1996年 | 10篇 |
1995年 | 12篇 |
1994年 | 7篇 |
1993年 | 9篇 |
1992年 | 14篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1976年 | 2篇 |
1975年 | 6篇 |
1968年 | 2篇 |
1960年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有712条查询结果,搜索用时 203 毫秒
91.
Díaz V Peinado AB Vleck VE Alvarez-Sánchez M Benito PJ Alves FB Calderón FJ Zapico AG 《Journal of strength and conditioning research / National Strength & Conditioning Association》2012,26(8):2209-2219
This study investigated the changes in cardiorespiratory response and running performance of 9 male "Talent Identification" (TID) and 6 male Senior Elite (SE) Spanish National Squad triathletes during a specific cycle-run (C-R) test. The TID and SE triathletes (initial age 15.2 ± 0.7 vs. 23.8 ± 5.6 years, p = 0.03; V(O2)max 77.0 ± 5.6 vs. 77.8 ± 3.6 ml · kg(-1) · min(-1), nonsignificant) underwent 3 tests through the competitive period and the preparatory period, respectively, of 2 consecutive seasons: test 1 was an incremental cycle test to determine the ventilatory threshold (Th(vent)); test 2 (C-R) was 30-minute constant load cycling at the Th(vent) power output followed by a 3-km time-trial run; and test 3 (isolated control run [R]) was an isolated 3-km time-trial control run, in randomized counterbalanced order. In both seasons, the time required to complete the C-R 3-km run was greater than for R in TID (11:09 ± 00:24 vs. 10:45 ± 00:16 min:ss, p < 0.01 and 10:24 ± 00:22 vs. 10:04 ± 00:14, p = 0.006, for season 2005-2006 and 2006-2007, respectively) and SE (10:15 ± 00:19 vs. 09:45 ± 00:30, p < 0.001 and 09:51 ± 00:26 vs. 09:46 ± 00:06, p = 0.02 for season 2005-2006 and 2006-2007, respectively). Compared with the first season, the completion of the time-trial run was faster in the second season (6.6%, p < 0.01 and 6.4%, p < 0.01, for C-R and R tests, respectively) only in TID. Changes in post cycling run performance were accompanied by changes in pacing strategy, but there were only slight or nonsignificant changes in the cardiorespiratory response. Thus, the negative effect of cycling on performance may persist, independently of the period, over 2 consecutive seasons in TID and SE triathletes; however, improvements over time suggests that monitoring running pacing strategy after cycling may be a useful tool to control performance and training adaptations in TID. 相似文献
92.
J Gagnaire O Dauwalder S Boisset D Khau AM Freydière F Ader M Bes G Lina A Tristan ME Reverdy A Marchand T Geissmann Y Benito G Durand JP Charrier J Etienne M Welker A Van Belkum F Vandenesch 《PloS one》2012,7(7):e40660
The aim of the present study was to detect the Staphylococcus aureus delta-toxin using Whole-Cell (WC) Matrix Assisted Laser Desorption Ionization-Time-of-Flight (MALDI-TOF) mass spectrometry (MS), correlate delta-toxin expression with accessory gene regulator (agr) status, and assess the prevalence of agr deficiency in clinical isolates with and without resistance to methicillin and glycopeptides. The position of the delta-toxin peak in the mass spectrum was identified using purified delta-toxin and isogenic wild type and mutant strains for agr-rnaIII, which encodes delta-toxin. Correlation between delta-toxin production and agr RNAIII expression was assessed by northern blotting. A series of 168 consecutive clinical isolates and 23 unrelated glycopeptide-intermediate S. aureus strains (GISA/heterogeneous GISA) were then tested by WC-MALDI-TOF MS. The delta-toxin peak was detected at 3005±5 Thomson, as expected for the naturally formylated delta toxin, or at 3035±5 Thomson for its G10S variant. Multivariate analysis showed that chronicity of S. aureus infection and glycopeptide resistance were significantly associated with delta-toxin deficiency (p?=?0.048; CI 95%: 1.01-10.24; p?=?0.023; CI 95%: 1.20-12.76, respectively). In conclusion, the S. aureus delta-toxin was identified in the WC-MALDI-TOF MS spectrum generated during routine identification procedures. Consequently, agr status can potentially predict infectious complications and rationalise application of novel virulence factor-based therapies. 相似文献
93.
JD Coso C González-Millán JJ Salinero J Abián-Vicén L Soriano S Garde B Pérez-González 《PloS one》2012,7(8):e43280
Background
To investigate the cause/s of muscle fatigue experienced during a half-iron distance triathlon.Methodology/Principal Findings
We recruited 25 trained triathletes (36±7 yr; 75.1±9.8 kg) for the study. Before and just after the race, jump height and leg muscle power output were measured during a countermovement jump on a force platform to determine leg muscle fatigue. Body weight, handgrip maximal force and blood and urine samples were also obtained before and after the race. Blood myoglobin and creatine kinase concentrations were determined as markers of muscle damage.Results
Jump height (from 30.3±5.0 to 23.4±6.4 cm; P<0.05) and leg power output (from 25.6±2.9 to 20.7±4.6 W · kg−1; P<0.05) were significantly reduced after the race. However, handgrip maximal force was unaffected by the race (430±59 to 430±62 N). Mean dehydration after the race was 2.3±1.2% with high inter-individual variability in the responses. Blood myoglobin and creatine kinase concentration increased to 516±248 µg · L−1 and 442±204 U · L−1, respectively (P<0.05) after the race. Pre- to post-race jump change did not correlate with dehydration (r = 0.16; P>0.05) but significantly correlated with myoglobin concentration (r = 0.65; P<0.001) and creatine kinase concentration (r = 0.54; P<0.001).Conclusions/significance
During a half-iron distance triathlon, the capacity of leg muscles to produce force was notably diminished while arm muscle force output remained unaffected. Leg muscle fatigue was correlated with blood markers of muscle damage suggesting that muscle breakdown is one of the most relevant sources of muscle fatigue during a triathlon. 相似文献94.
95.
Perret M Badiou C Lina G Burbaud S Benito Y Bes M Cottin V Couzon F Juruj C Dauwalder O Goutagny N Diep BA Vandenesch F Henry T 《Cellular microbiology》2012,14(7):1019-1036
Staphylococcus aureus is a major pathogen responsible for both nosocomial and community-acquired infections. Central to its virulence is its ability to secrete haemolysins, pore-forming toxins and cytolytic peptides. The large number of membrane-damaging toxins and peptides produced during S. aureus infections has hindered a precise understanding of their specific roles in diseases. Here, we used comprehensive libraries of recombinant toxins and synthetic cytolytic peptides, of S. aureus mutants and clinical strains to investigate the role of these virulence factors in targeting human macrophages and triggering IL-1β release. We found that the Panton Valentine leukocidin (PVL) is the major trigger of IL-1β release and inflammasome activation in primary human macrophages. The cytolytic peptides, δ-haemolysin and PSMα3; the pore-forming toxins, γ-haemolysin and LukDE; and β-haemolysin synergize with PVL to amplify IL-1β release, indicating that these factors cooperate with PVL to trigger inflammation. PVL(+) S. aureus causes necrotizing pneumonia in children and young adults. The severity of this disease is due to the massive recruitment of neutrophils that cause lung damage. Importantly, we demonstrate that PVL triggers IL-1β release in human alveolar macrophages. Furthermore, IL-1β released by PVL-intoxicated macrophages stimulates the secretion of the neutrophil attracting chemokines, IL-8 and monocyte chemotactic protein-1, by lung epithelial cells. Finally, we show that PVL-induced IL-8/monocyte chemotactic protein-1 release is abolished by the inclusion of IL-1 receptor antagonist (IL-1Ra) in a mixed culture of lung epithelial cells and macrophages. Together, our results identify PVL as the predominant S. aureus secreted factor for triggering inflammasome activation in human macrophages and demonstrate how PVL-intoxicated macrophages orchestrate inflammation in the lung. Finally, our work suggests that anakinra, a synthetic IL-1Ra, may be an effective therapeutic agent to reduce the massive neutrophils infiltration observed during necrotizing pneumonia and decrease the resulting host-mediated lung injury. 相似文献
96.
Seth M Dever E Railey White Matthew CT Hartman Kristoffer Valerie 《Cell cycle (Georgetown, Tex.)》2012,11(4):687-694
Despite intense studies, questions still remain regarding the molecular mechanisms leading to the development of hereditary breast and ovarian cancers. Research focused on elucidating the role of the breast cancer susceptibility gene 1 (BRCA1) in the DNA damage response may be of the most critical importance to understanding these processes. The BRCA1 protein has an N-terminal RING domain possessing E3 ubiquitin-ligase activity and a C-terminal BRCT domain involved in binding specific phosphoproteins. These domains are involved directly or indirectly in DNA double-strand break (DSB) repair. As the two terminal domains of BRCA1 represent two separate entities, understanding how these domains communicate and are functionally altered in regards to DSB repair is critical for understanding the development of BRCA1-related breast and ovarian cancers and for developing novel therapeutics. Herein, we review recent findings of how altered functions of these domains might lead to cancer through a mechanism of increased aberrant homologous recombination and possible implications for the development of BRCA1 inhibitors.Key words: BRCT, DNA repair, peptide, radiation, RING, ubiquitylation 相似文献
97.
Bacillus subtilis gene yshC encodes a 64-kDa family X DNA polymerase (PolXBs), which contains all the critical residues involved in DNA and nucleotide binding as well as those responsible for catalysis of DNA polymerization, conserved in most family X members. Biochemical analyses of the purified enzyme indicate that PolXBs is a monomeric and strictly template-directed DNA polymerase, preferentially acting on DNA structures containing gaps from one to a few nucleotides and bearing a phosphate group at the 5' end of the downstream DNA. The fact that PolXBs is able to conduct filling of a single-nucleotide gap, allowing further sealing of the resulting nick by a DNA ligase, points to a putative role in base excision repair during the B. subtilis life cycle. 相似文献
98.
Aims: To determine if pretreatment with oxidizing agents sensitizes Bacillus subtilis spores to dry heat or desiccation. Methods: Bacillus subtilis spores were killed approx. 90% by oxidizing agents, and the sensitivity of treated and untreated spores to dry heat and desiccation was determined. The effects of pyruvate on spore recovery after oxidizing agent pretreatment and then dry heat or desiccation were also determined. Conclusions: Spores pretreated with Oxone? or hypochlorite were not sensitized to dry heat or freeze‐drying. However, hydrogen peroxide or t‐butylhydroperoxide pretreatment sensitized spores to dry heat or desiccation, and the desiccation caused mutagenesis in the survivors. Pyruvate increased recovery of spores treated with hydrogen peroxide alone or plus dry heat or desiccation, and with t‐butylhydroperoxide and desiccation, but not with t‐butylhydroperoxide alone or plus dry heat. Significance and Impact of the Study: Pretreatment with peroxides sensitizes bacterial spores to subsequent stress. This finding may suggest improved regimens for spore inactivation. 相似文献
99.
Gastañaga Ugarte M Sánchez Sánchez J Rodríguez Borrego R Rodrigo Rodríguez M Benito Díaz J 《Revista espa?ola de geriatría y gerontología》2008,43(1):55-59
We describe the diagnosis of a large paraesophageal hernia that showed a risk of torsion in an 84-year-old man who had good health status and no clinical antecedents of interest until the previous night when he woke up and felt dyspnea, some pain located in the epigastrium and a fever spike. After a short interview with ambiguous and inconclusive answers, the main diagnosis was based on the data obtained from the physical examination, the electrocardiogram, the results of the emergency blood tests, and the hydroaerial level that appeared on the standing chest x-ray; acute myocardial infarction and pulmonary embolism were excluded. Once the patient was stabilized, esophagogastroscopy was requested and some hours later the patient underwent the remaining examinations: intestinal transit, opaque enema and computed tomography scan, which are described in the text. The results of these examinations form the basis of a generic discussion about this case and a literature review from point of view of geriatrics. Few cases of large diaphragmatic hernias in octogenarians have been reported in the literature. We discuss the contribution of the techniques used in the diagnosis of this entity. 相似文献
100.
Insulin resistant states are associated with an increase in the beta cell mass and also high levels of circulating insulin. Ultimately the beta cells undergo a failure that leads to diabetes. At this stage, a question arises if those persistent high levels of circulating insulin may contribute to beta cell damage. To address this important issue, we submitted beta cells to a prolonged effect of increasing concentrations of insulin. We observed that a prolonged effect of high levels of insulin on the presence of serum (15-24 h) in glucose-deprived beta cells induced apoptosis. This apoptotic effect was both dose- and cycloheximide-dependent. 相似文献