全文获取类型
收费全文 | 1254篇 |
免费 | 84篇 |
国内免费 | 1篇 |
出版年
2022年 | 12篇 |
2021年 | 20篇 |
2020年 | 15篇 |
2019年 | 18篇 |
2018年 | 22篇 |
2017年 | 18篇 |
2016年 | 38篇 |
2015年 | 59篇 |
2014年 | 58篇 |
2013年 | 76篇 |
2012年 | 93篇 |
2011年 | 65篇 |
2010年 | 37篇 |
2009年 | 50篇 |
2008年 | 60篇 |
2007年 | 60篇 |
2006年 | 64篇 |
2005年 | 50篇 |
2004年 | 50篇 |
2003年 | 41篇 |
2002年 | 48篇 |
2001年 | 6篇 |
2000年 | 9篇 |
1999年 | 15篇 |
1998年 | 22篇 |
1997年 | 17篇 |
1996年 | 15篇 |
1995年 | 21篇 |
1994年 | 20篇 |
1993年 | 12篇 |
1992年 | 20篇 |
1991年 | 11篇 |
1990年 | 15篇 |
1989年 | 8篇 |
1988年 | 5篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 12篇 |
1981年 | 18篇 |
1980年 | 10篇 |
1979年 | 11篇 |
1978年 | 9篇 |
1977年 | 11篇 |
1976年 | 12篇 |
1975年 | 14篇 |
1974年 | 12篇 |
1973年 | 7篇 |
1971年 | 8篇 |
1970年 | 5篇 |
1967年 | 8篇 |
排序方式: 共有1339条查询结果,搜索用时 19 毫秒
131.
Neutrophil elastase sorting involves plasma membrane trafficking requiring the C-terminal propeptide
Tapper H Källquist L Johnsson E Persson AM Hansson M Olsson I 《Experimental cell research》2006,312(18):3471-3484
The primary granules/secretory lysosomes of neutrophils store mature neutrophil elastase (NE) as a luminal protein after proteolytic removal of N-terminal and C-terminal pro-peptides from a proform of NE. The N-terminal pro-peptide prevents premature activation that might be toxic to the cell, but the C-terminal pro-peptide has no defined function. In this study, we investigated the role of the C-terminal pro-peptide in trafficking of NE by expressing, in rat basophilic leukemia (RBL) cells, both wild-type NE and the mutant NE/Delta248-267, which lacks the C-terminal pro-peptide. Both transfected proteins were found to be targeted to secretory lysosomes. In addition, results from antibody ligation and cell-surface biotinylation indicated that proform of NE was targeted to the plasma membrane, and then subjected to endocytosis. The results were supported by the detection of targeting of the proform to the plasma membrane followed by internalization both in RBL cells and normal granulopoietic precursor cells. Targeting of NE to the plasma membrane required the C-terminal pro-peptide as NE/Delta248-267 expressed in RBL cells bypassed plasma membrane trafficking. Our results indicate targeting of a population of NE to the plasma membrane and internalization dependent on the C-terminal NE pro-peptide. 相似文献
132.
Harbeck M Dobberstein R Ritz-Timme S Schröder I Grupe G 《Anthropologischer Anzeiger; Bericht über die biologisch-anthropologische Literatur》2006,64(3):273-282
Modern bone samples were experimentally degraded by incubation into water at increased temperature and examined in terms of their collagen content, the stable C and N isotopic ratios, and the molar C/N ratio. The same analyses were carried out with archaeological human bone of varying age (300 up to 8000 years). The experimentally degraded samples exhibited changes of the collagen's integrity, which influence the stable isotope ratios. In the case of the archaeological material, a correlation between stable delta13C- and delta15N-values and collagen content could be demonstrated. The molar C:N ratio was no suitable criterion for the assessment of the state of preservation of extractable collagen. 相似文献
133.
Vrazić H Sikić J Lucijanić T Milosević M Borić K Udovicić M Cmrecnjak J Heim I Gostović MJ Bergovec M 《Collegium antropologicum》2012,36(Z1):229-233
The aim of this paper was to investigate the prevalence of smoking using selected anthropometric variables in a sample of hospitalized coronary heart disease (CHD) patients in Croatia (N = 1,298). A total of 444 subjects (34.6%) were non-smokers, 548 (42.6%) were smokers and 293 (22.8%) were ex-smokers. Men, on average, smoked more cigarettes per day than women (22.62 vs. 19.84 cigarettes, p < 0.001) and they also had bigger index "pack-years" than women (36.96 vs. 33.91, p = 0.024). Men were more often smokers and ex-smokers than women (47.4% vs. 30.8% for smokers and 25.0% vs. 22.8% for ex-smokers, p < 0.001). In this study a high prevalence of smoking was found among CHD patients in Croatia. Unless it is decreased, it can be expected that CHD patients in Croatia will continue to experience adverse effects more often than other CHD patients in the rest of Europe. 相似文献
134.
Goekint M Bos I Heyman E Meeusen R Michotte Y Sarre S 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,112(4):535-541
Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and monoamine neurotransmission is known to increase with exercise. The purpose of this study was to examine the influence of acute exercise on monoaminergic neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was performed in rats that were subjected to 60 min of treadmill running at 20 m/min or rest. Two hours postexercise, the rats were killed, and the hippocampus was dissected. In experiments without microdialysis, hippocampus and serum samples were collected immediately after exercise. Exercise induced a twofold increase in hippocampal dopamine release. Noradrenaline and serotonin release were not affected. Hippocampal BDNF levels were not influenced, whether they were measured immediately or 2 h after the exercise protocol. Serum BDNF levels did not change either, but serum BDNF was negatively correlated to peripheral corticosterone concentrations, indicating a possible inhibitory reaction to the stress of running. Sixty minutes of exercise enhances dopamine release in the hippocampus of the rat in vivo. However, this increase is not associated with changes in BDNF protein levels immediately nor 2 h after the acute exercise bout. An increased corticosterone level might be the contributing factor for the absence of changes in BDNF. 相似文献
135.
Neubauer K Hühns M Hausmann T Klemke F Lockau W Kahmann U Pistorius EK Kragl U Broer I 《Journal of biotechnology》2012,158(1-2):50-58
A chimeric cyanophycin synthetase gene composed of the cphATe coding region from the cyanobacterium Thermosynechococcus elongatus BP-1, the constitutive 35S promoter and the plastid targeting sequence of the integral photosystem II protein PsbY was transferred to the tobacco variety Petit Havanna SRI and the commercial potato starch production variety Albatros. The resulting constitutive expression of cyanophycin synthetase leads to polymer contents in potato leaf chloroplasts of up to 35 mg/g dry weight and in tuber amyloplasts of up to 9 mg/g dry weight. Both transgenic tobacco and potato were used for the development of isolation methods applicable for large-scale extraction of the polymer. Two different procedures were developed which yielded polymer samples of 80 and 90% purity, respectively. 相似文献
136.
Gualano B Everaert I Stegen S Artioli GG Taes Y Roschel H Achten E Otaduy MC Junior AH Harris R Derave W 《Amino acids》2012,43(1):21-24
Carnosine is present in high concentrations in skeletal muscle where it contributes to acid buffering and functions also as a natural protector against oxidative and carbonyl stress. Animal studies have shown an anti-diabetic effect of carnosine supplementation. High carnosinase activity, the carnosine degrading enzyme in serum, is a risk factor for diabetic complications in humans. The aim of the present study was to compare the muscle carnosine concentration in diabetic subjects to the level in non-diabetics. Type 1 and 2 diabetic patients and matched healthy controls (total n=58) were included in the study. Muscle carnosine content was evaluated by proton magnetic resonance spectroscopy (3 Tesla) in soleus and gastrocnemius. Significantly lower carnosine content (-45%) in gastrocnemius muscle, but not in soleus, was shown in type 2 diabetic patients compared with controls. No differences were observed in type 1 diabetic patients. Type II diabetic patients display a reduced muscular carnosine content. A reduction in muscle carnosine concentration may be partially associated with defective mechanisms against oxidative, glycative and carbonyl stress in muscle. 相似文献
137.
138.
Kieffer TL De Meyer S Bartels DJ Sullivan JC Zhang EZ Tigges A Dierynck I Spanks J Dorrian J Jiang M Adiwijaya B Ghys A Beumont M Kauffman RS Adda N Jacobson IM Sherman KE Zeuzem S Kwong AD Picchio G 《PloS one》2012,7(4):e34372
Background
In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR.Methods
Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment.Results
Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients.Conclusions
A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment. 相似文献139.
de Rooij MM Schimmer B Versteeg B Schneeberger P Berends BR Heederik D van der Hoek W Wouters IM 《PloS one》2012,7(2):e32108
Background
Q fever is an occupational risk for veterinarians, however little is known about the risk for veterinary medicine students. This study aimed to assess the seroprevalence of Coxiella burnetii among veterinary medicine students and to identify associated risk factors.Methods
A cross-sectional study with questionnaire and blood sample collection was performed among all veterinary medicine students studying in the Netherlands in 2006. Serum samples (n = 674), representative of all study years and study directions, were analyzed for C. burnetii IgG and IgM phase I and II antibodies with an immunofluorescence assay (IFA). Seropositivity was defined as IgG phase I and/or II titer of 1∶32 and above.Results
Of the veterinary medicine students 126 (18.7%) had IgG antibodies against C. burnetii. Seropositivity associated risk factors identified were the study direction ‘farm animals’ (Odds Ratio (OR) 3.27 [95% CI 2.14–5.02]), advanced year of study (OR year 6: 2.31 [1.22–4.39] OR year 3–5 1.83 [1.07–3.10]) having had a zoonosis during the study (OR 1.74 [1.07–2.82]) and ever lived on a ruminant farm (OR 2.73 [1.59–4.67]). Stratified analysis revealed study direction ‘farm animals’ to be a study-related risk factor apart from ever living on a farm. In addition we identified a clear dose-response relation for the number of years lived on a farm with C. burnetii seropositivity.Conclusions
C. burnetii seroprevalence is considerable among veterinary medicine students and study related risk factors were identified. This indicates Q fever as an occupational risk for veterinary medicine students. 相似文献140.