全文获取类型
收费全文 | 618篇 |
免费 | 34篇 |
专业分类
652篇 |
出版年
2023年 | 4篇 |
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 9篇 |
2018年 | 14篇 |
2017年 | 5篇 |
2016年 | 16篇 |
2015年 | 27篇 |
2014年 | 26篇 |
2013年 | 49篇 |
2012年 | 40篇 |
2011年 | 60篇 |
2010年 | 32篇 |
2009年 | 25篇 |
2008年 | 25篇 |
2007年 | 34篇 |
2006年 | 31篇 |
2005年 | 35篇 |
2004年 | 41篇 |
2003年 | 23篇 |
2002年 | 26篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 10篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1991年 | 4篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1933年 | 2篇 |
1930年 | 1篇 |
1908年 | 1篇 |
1897年 | 2篇 |
1896年 | 1篇 |
排序方式: 共有652条查询结果,搜索用时 15 毫秒
41.
Antonella Del Corso Pier Giuseppe Vilardo Mario Cappiello Ilaria Cecconi Massimo Dal Monte Daniela Barsacchi Umberto Mura 《Archives of biochemistry and biophysics》2002,397(2):392-398
Glutathione is one of the most relevant antioxidants present in cells. It exerts its scavenging action through the involvement of efficient and ubiquitous enzymes. GSH on the other hand, because of its chemical features, can scavenge reactive oxygen species without the involvement of enzymatic systems. The study deals with the mobilization of GSH pool in a nonenzymatic antioxidant system by other physiological thiols (i.e., cysteine and cysteinyl-glycine), which are far more sensitive than GSH to oxidative conditions. These thiol compounds, in the presence of iron/EDTA, can promote oxygen activation through their oxidation to disulfides. GSH, through trans-thiolation reactions, can regenerate Cys and CysGly, which can then recycle, thus inducing a massive GSH oxidation. In these conditions, making use of bovine lens aldose reductase as a protein model, evidence is given that Cys and CysGly promote specific protein S-thiolation reactions. The possibility that GSH may be recruited in controlling cellular oxygen tension is considered. 相似文献
42.
Oxidative stress in diabetes-induced endothelial dysfunction involvement of nitric oxide and protein kinase C 总被引:3,自引:0,他引:3
Pricci F Leto G Amadio L Iacobini C Cordone S Catalano S Zicari A Sorcini M Di Mario U Pugliese G 《Free radical biology & medicine》2003,35(6):683-694
Reactive oxygen species (ROS) formation plays a major role in diabetes-induced endothelial dysfunction, though the molecular mechanism(s) involved and the contribution of nitric oxide (NO) are still unclear. This study using bovine retinal endothelial cells was aimed at assessing (i) the role of oxygen-dependent vs. NO-dependent oxidative stress in the endothelial cell permeability alterations induced by the diabetic milieu and (ii) whether protein kinase C (PKC) activation ultimately mediates these changes. Superoxide, lipid peroxide, and PKC activity were higher under high glucose (HG) vs. normal glucose throughout the 30 d period. Nitrite/nitrate and endothelial NO synthase levels increased at 1 d and decreased thereafter. Changes in monolayer permeability to 125I-BSA induced by 1 or 30 d incubation in HG or exposure to advanced glycosylation endproduct were reduced by treatment with antioxidants or PKC inhibitors, whereas NO blockade prevented only the effect of 1 d HG. HG-induced changes were mimicked by a PKC activator, a superoxide generating system, an NO and superoxide donor, or peroxynitrite (attenuated by PKC inhibition), but not a NO donor. The short-term effect of HG depends on a combined oxidative and nitrosative stress with peroxynitrite formation, whereas the long-term effect is related to ROS generation; in both cases, PKC ultimately mediates permeability changes. 相似文献
43.
Santucci M Portaccio M Eldin MS Pagliuca N Rossi S Bencivenga U Gaeta FS Mita DG 《Enzyme and microbial technology》2000,26(8):593-601
The dynamic and steady-state responses as well as the response times of a glucose biosensor have been studied under isothermal and non-isothermal conditions as a function of analyte concentration. The presence of a temperature gradient across the catalytic membrane system improved the biosensor characteristics, because the dynamic and steady-state responses increased and the response times decreased under non-isothermal conditions. For example, a macroscopic temperature difference of 20 degrees C applied across the catalytic membrane system increases the biosensor sensitivity of 70% and reduces of 50% its response time. The dependence of the observed effects on the magnitude of the temperature difference applied has been correlated with the substrate (and products) transport across the catalytic membrane system due to the process of thermodialysis. 相似文献
44.
Cristina Sotgia Umberto Fascio Roberta Pennati Fiorenza De Bernardi 《Development, growth & differentiation》1998,40(1):75-84
Animal caps isolated from Xenopus laevis embryos at the blastula stage were treated sequentially with NH4 Cl, a known cement gland inducer, and with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a known neural inducer. The two artificial inducers were also used in reverse order to see if they can mimic the natural inducers acting during the progressive determination of the ectodermal organ. Immunofluorescence and whole-mount in situ hybridization were used to study the expression of tubulin, taken to indicate an early step on the pathway of cell elongation, and neural cell adhesion molecule (N-CAM) taken to indicate an early step in the determination of the nervous system. The expression of XCG-1, a marker of early specification of the cement gland, was also studied. The results showed that the two artificial inducers can mimic the effects of the natural inducers in animal cap explants. The TPA behaves like a neural inducer, reducing the number and the extension of the cement gland when added to the medium in addition to NH4 Cl, before or after NH4 Cl treatment. In the process of cement gland/neural induction, it is possible to redirect the ectoderm already specified as cement gland to neural tissue, but it does not seem possible to respecify the neural tissue as cement gland. Moreover, the animal caps were also cut into dorsal and ventral parts and the two halves were treated separately. The results were similar to those obtained with treatment of the entire animal cap, suggesting that a dorsal-ventral pattern is not yet established before the gastrula stage, and that in normal embryos there are boundaries between the effects of different inducers. 相似文献
45.
Gian Carlo Manicardi Antonella Tombacco Davide Bizzaro Umberto Bianchi Patrizia Grace Bianchi Denny Sakkas 《The Histochemical journal》1998,30(1):33-39
The nick translation and terminal transferase assays have been compared to test their relative efficiency in detecting DNA breakage in ejaculated human spermatozoa. The results have been correlated with the percentage of chromomycin A3 positive sperm, a fluorochrome that is indicative of the protamination state of sperm. Examination of the ejaculated sperm of 30 subjects revealed that the percentage of positivity to the nick translation and terminal transferase assays did not differ, even when using different fixatives. It is concluded that the inability of the two assays to distinguish the type of DNA damage, as is possible in somatic nuclei, is most probably linked to the unique nature of sperm chromatin. It is proposed that the presence of the damaged DNA may be the remnants of an imperfect spermiogenesis, probably related to an inadequate protamine deposition. This is supported by the strong correlation between the presence of DNA damage and underprotamination as evidenced by chromomycin A3. © Chapman & Hall 相似文献
46.
Marco Salemi Anne-Mieke Vandamme Chiara Gradozzi Kristel Van Laethem Ercole Cattaneo Graham Taylor Claudio Casoli Patrick Goubau Jan Desmyter Umberto Bertazzoni 《Journal of molecular evolution》1998,46(5):602-611
Seven new Italian and two new British HTLV-II isolates were obtained from injecting drug users and the entire long terminal
repeat (LTR) region was sequenced. Restriction analysis showed that all the Italian isolates are of the IIb subtype, whereas
the British isolates are of the IIa subtype. To understand whether the further differentiation of each two principal HTLV-II
subtypes in several subgroups could be statistically supported by phylogenetic analysis, the neighbor-joining, parsimony,
and maximum likelihood methods were used. The separation between IIa and IIb is very well supported by all three methods.
At least two phylogenetic subgroups exist within the HTLV-IIa and at least three within the HTLV-IIb subtype. In the present
analysis, no statistical support was obtained for additional phylogroups. Two particular subgroups seem interesting because
they include all European and North American injecting drug user strains within the IIa and IIb subtypes, respectively. These
data confirm that European HTLV-II infection among drug users is probably derived from North America. They also suggest that
though a certain differentiation by restriction analysis in different subgroups is possible, carefully interpreted phylogenetic
analyses remain necessary. Using the likelihood ratio test, a molecular clock for the drug user strains was calibrated. A
fixation rate between 1.08 × 10−4 and 2.7 × 10−5 nucleotide substitutions per site per year was calculated for the IIa and IIb injecting drug user strains. This is the lowest
fixation rate so far reported for RNA viruses, including for HIV, which typically range between 10−2 and 10−4. 相似文献
47.
Elisa Damiani Erica Adrario Michele Maria Luchetti Claudia Scorcella Andrea Carsetti Nicoletta Mininno Silvia Pierantozzi Tiziana Principi Daniele Strovegli Rosella Bencivenga Armando Gabrielli Rocco Romano Paolo Pelaia Can Ince Abele Donati 《PloS one》2015,10(5)
BackgroundFree hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected.MethodsThis is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (<10 or >15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.ResultsSimilar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098–0.219] mg/mL to 0.238 [0.163–0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003).ConclusionsOld RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.
Trial Registration
ClinicalTrials.gov NCT01584999相似文献48.
Marc Guaita Umberto Melia Montserrat Vallverdú Pere Caminal Isabel Vilaseca Josep M. Montserrat Carles Gaig Manel Salamero Joan Santamaria 《PloS one》2015,10(4)
Aim
The present study aimed to analyse the autonomic nervous system activity using heart rate variability (HRV) to detect sleep disordered breathing (SDB) patients with and without excessive daytime sleepiness (EDS) before sleep onset.Methods
Two groups of 20 patients with different levels of daytime sleepiness -sleepy group, SG; alert group, AG- were selected consecutively from a Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT) research protocol. The first waking 3-min window of RR signal at the beginning of each nap test was considered for the analysis. HRV was measured with traditional linear measures and with time-frequency representations. Non-linear measures -correntropy, CORR; auto-mutual-information function, AMIF- were used to describe the regularity of the RR rhythm. Statistical analysis was performed with non-parametric tests.Results
Non-linear dynamic of the RR rhythm was more regular in the SG than in the AG during the first wakefulness period of MSLT, but not during MWT. AMIF (in high-frequency and in Total band) and CORR (in Total band) yielded sensitivity > 70%, specificity >75% and an area under ROC curve > 0.80 in classifying SG and AG patients.Conclusion
The regularity of the RR rhythm measured at the beginning of the MSLT could be used to detect SDB patients with and without EDS before the appearance of sleep onset. 相似文献49.
Marc C. Tahita Halidou Tinto Annette Erhart Adama Kazienga Robert Fitzhenry Chantal VanOvermeir Anna Rosanas-Urgell Jean-Bosco Ouedraogo Robert T. Guiguemde Jean-Pierre Van geertruyden Umberto D’Alessandro 《PloS one》2015,10(9)
Background
The emergence and spread of drug resistance represents one of the biggest challenges for malaria control in endemic regions. Sulfadoxine-pyrimethamine (SP) is currently deployed as intermittent preventive treatment in pregnancy (IPTp) to prevent the adverse effects of malaria on the mother and her offspring. Nevertheless, its efficacy is threatened by SP resistance which can be estimated by the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations. This was measured among pregnant women in the health district of Nanoro, Burkina Faso.Methods
From June to December 2010, two hundred and fifty six pregnant women in the second and third trimester, attending antenatal care with microscopically confirmed malaria infection were invited to participate, regardless of malaria symptoms. A blood sample was collected on filter paper and analyzed by PCR-RFLP for the alleles 51, 59, 108, 164 in the pfdhfr gene and 437, 540 in the pfdhps gene.Results
The genes were successfully genotyped in all but one sample (99.6%; 255/256) for dhfr and in 90.2% (231/256) for dhps. The dhfr C59R and S108N mutations were the most common, with a prevalence of 61.2% (156/255) and 55.7% (142/255), respectively; 12.2% (31/255) samples had also the dhfr N51I mutation while the I164L mutation was absent. The dhps A437G mutation was found in 34.2% (79/231) isolates, but none of them carried the codon K540E. The prevalence of the dhfr double mutations NRNI and the triple mutations IRNI was 35.7% (91/255) and 11.4% (29/255), respectively.Conclusion
Though the mutations in the pfdhfr and pfdhps genes were relatively common, the prevalence of the triple pfdhfr mutation was very low, indicating that SP as IPTp is still efficacious in Burkina Faso. 相似文献50.
Ifedayo M. O. Adetifa Abdul Khalie Muhammad David Jeffries Simon Donkor Martien W. Borgdorff Tumani Corrah Umberto D’Alessandro 《PloS one》2015,10(10)