全文获取类型
收费全文 | 1042篇 |
免费 | 67篇 |
出版年
2023年 | 4篇 |
2022年 | 16篇 |
2021年 | 17篇 |
2020年 | 16篇 |
2019年 | 30篇 |
2018年 | 33篇 |
2017年 | 16篇 |
2016年 | 47篇 |
2015年 | 64篇 |
2014年 | 64篇 |
2013年 | 84篇 |
2012年 | 81篇 |
2011年 | 99篇 |
2010年 | 55篇 |
2009年 | 36篇 |
2008年 | 59篇 |
2007年 | 80篇 |
2006年 | 62篇 |
2005年 | 49篇 |
2004年 | 40篇 |
2003年 | 42篇 |
2002年 | 28篇 |
2001年 | 5篇 |
2000年 | 8篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 17篇 |
1995年 | 4篇 |
1994年 | 11篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有1109条查询结果,搜索用时 15 毫秒
21.
Gloria Taliani Martina Spaziante Elisa Biliotti Marina Borro Donatella Palazzo Stefania Grieco Cristiana Franchi Giancarlo Iaiani Caterina Furlan Valentina Gallinaro Maurizio Simmaco 《PloS one》2013,8(8)
Background
Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients.Aims
The aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects.Methods and patients
We enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects.Results
CC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p = 0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p = 0.02). Hepatic steatosis did not correlate with IL28B genotype (p = 0,14) but only with a high body mass index (BMI) value (p = 0.03).Conclusions
Female subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile. 相似文献22.
Silvia Rossi Valeria Studer Alessandro Moscatelli Caterina Motta Giancarlo Coghe Giuseppe Fenu Stacy Caillier Fabio Buttari Francesco Mori Francesca Barbieri Maura Castelli Valentina De Chiara Fabrizia Monteleone Raffaele Mancino Giorgio Bernardi Sergio E. Baranzini Maria G. Marrosu Jorge R. Oksenberg Diego Centonze 《PloS one》2013,8(6)
Synaptic transmission and plasticity mediated by NMDA receptors (NMDARs) could modulate the severity of multiple sclerosis (MS). Here the role of NMDARs in MS was first explored in 691 subjects carrying specific allelic variants of the NR1 subunit gene or of the NR2B subunit gene of this glutamate receptor. The analysis was replicated for significant SNPs in an independent sample of 1548 MS subjects. The C allele of rs4880213 was found to be associated with reduced NMDAR-mediated cortical excitability, and with increased probability of having more disability than the CT/TT MS subjects. MS severity was higher in the CC group among relapsing-remitting MS (RR-MS) patients, while primary progressive MS (PP-MS) subjects homozygous for the T allele had more pronounced clinical worsening. Mean time to first relapse, but not to an active MRI scan, was lower in the CC group of RR-MS patients, and the number of subjects with two or more clinical relapses in the first two years of the disease was higher in CC compared to CT/TT group. Furthermore, the percentage of relapses associated with residual disability was lower in subjects carrying the T allele. Lesion load at the MRI was conversely unaffected by the C or T allele of this SNP in RR-MS patients. Axonal and neuronal degeneration at the optical coherence tomography was more severe in the TT group of PP-MS patients, while reduced retinal nerve fiber thickness had less consequences on visual acuity in RR-MS patients bearing the T allele. Finally, the T allele was associated with preserved cognitive abilities at the Rao’s brief repeatable neuropsychological battery in RR-MS. Signaling through glutamate NMDARs enhances both compensatory synaptic plasticity and excitotoxic neurodegeneration, impacting in opposite ways on RR-MS and PP-MS pathophysiological mechanisms. 相似文献
23.
Mohammed O. Abdelaziz Celestino Bonura Aurora Aleo Teresa Fasciana Cinzia Calà Caterina Mammina 《Microbiology and immunology》2013,57(5):391-395
Cephalosporin‐resistant Escherichia coli has been increasingly reported worldwide. In this study, 32 cephalosporin resistant E. coli isolates identified from cancer patients in Cairo, Egypt in 2009–2010 were analyzed. Twenty‐three were of phylogenetic group D, seven A and one each B1 and B2. By rep‐PCR 15 phylogroup D isolates were grouped in four clusters, one with sequence type (ST) 405 and three ST68. Seventeen isolates showed single patterns. blaCTX‐M‐15 and aac(6')‐Ib‐cr were the most common resistance determinants. blaOXA‐48 and blaVIM were also detected. Multidrug resistant E. coli seriously affects healthcare, especially in immunocompromised hosts, such as cancer patients. 相似文献
24.
25.
26.
Fluoro‐Sorafenib (Regorafenib) effects on hepatoma cells: Growth inhibition,quiescence, and recovery
Brian I. Carr Aldo Cavallini Catia Lippolis Rosalba D'Alessandro Caterina Messa Maria G. Refolo Angela Tafaro 《Journal of cellular physiology》2013,228(2):292-297
To evaluate the growth‐inhibitory properties of the potent multi‐kinase antagonist Regorafenib (Fluoro‐Sorafenib), which was synthesized as a more potent Sorafenib, a Raf inhibitor and to determine whether similar mechanisms were involved, human hepatoma cell lines were grown in the presence or absence of Regorafanib and examined for growth inhibition. Western blots were performed for Raf targets, apoptosis, and autophagy. Regorafenib inhibited growth of human Hep3B, PLC/PRF/5, and HepG2 cells in a concentration‐ and time‐dependent manner. Multiple signaling pathways were altered, including MAP kinases phospho‐ERK and phospho‐JNK and its target phospho‐c‐Jun. There was evidence for apoptosis by FACS, cleavage of caspases and increased Bax levels; as well as induction of autophagy, as judged by increased Beclin‐1 and LC3 (II) levels. Prolonged drug exposure resulted in cell quiescence. Full growth recovery occurred after drug removal, unlike with doxorubicin chemotherapy. Regorafenib is a potent inhibitor of cell growth. Cells surviving Regorafenib treatment remain viable, but quiescent and capable of regrowth following drug removal. The reversibility of tumor cell growth suppression after drug removal may have clinical implications. J. Cell. Physiol. 228: 292–297, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
27.
28.
29.
Maria Teresa Montagna Caterina Coretti Antonella Rella Giovanna Barbuti Fabio Manca Osvaldo Montagna Nicola Laforgia Giuseppina Caggiano 《Folia microbiologica》2013,58(1):27-31
Candidemia is a major infectious complication in neonatal patients. The isolation of yeasts from blood is still the ??gold standard?? for its diagnosis, but other laboratory markers (i.e., circulating antigens) have been studied with varying specificities and sensitivities. The aim of this study was to evaluate the role of procalcitonin for the diagnosis of candidemia in neonatal patients at high risk. To verify if the use of different commercial methods can highlight dissimilar results of sensitivity and/or specificity, the determination of procalcitonin serum levels was estimated by two systems. Overall, 90 patients from a Neonatal Intensive Care Units were enrolled, of whom six developed Candida bloodstream infection. Four of six infants with candidemia had slight increase of procalcitonin values (0.5?C1?ng/mL). Only one baby showed very high levels but he had fungal and bacterial sepsis at the same time, while no elevation was observed in the sixth patient. No statistically significant difference was observed between two different methods at the time of monitoring (p?>?0.643). Both methods showed a sensitivity of 83.3?% at diagnosis, while the specificity was 73.8 and 63.1?% by methods A and B, respectively. In the light of the low sensibility and specificity of this assay, we can assume that the determination of procalcitonin would not seem to play a significant role in the diagnosis of fungal infection in neonatal patients. 相似文献
30.
Federica Vacondio Caterina Carmi Elena Galvani Michele Bassi Claudia Silva Alessio Lodola Silvia Rivara Andrea Cavazzoni Roberta R. Alfieri Pier Giorgio Petronini Marco Mor 《Bioorganic & medicinal chemistry letters》2013,23(19):5290-5294
In the present study, a small set of reversible or irreversible 4-anilinoquinazoline EGFR inhibitors was tested in A549 cells at early (1 h) and late (8 h) time points after inhibitor removal from culture medium. A combination of assays was employed to explain the observed long-lasting inhibition of EGFR autophosphorylation. We found that EGFR inhibition at 8 h can be due, besides to the covalent interaction of the inhibitor with Cys797, as for PD168393 (2) and its prodrug 4, to the intracellular accumulation of non-covalent inhibitors by means of an active cell uptake, as for 5 and 6. Compounds 5–6 showed similar potency and duration of inhibition of EGFR autophosphorylation as the covalent inhibitor 2, while being devoid of reactive groups forming covalent bonds with protein thiols. 相似文献