全文获取类型
收费全文 | 2582篇 |
免费 | 182篇 |
出版年
2023年 | 9篇 |
2022年 | 19篇 |
2021年 | 33篇 |
2020年 | 27篇 |
2019年 | 25篇 |
2018年 | 50篇 |
2017年 | 47篇 |
2016年 | 75篇 |
2015年 | 105篇 |
2014年 | 122篇 |
2013年 | 189篇 |
2012年 | 192篇 |
2011年 | 176篇 |
2010年 | 136篇 |
2009年 | 128篇 |
2008年 | 173篇 |
2007年 | 159篇 |
2006年 | 160篇 |
2005年 | 125篇 |
2004年 | 153篇 |
2003年 | 115篇 |
2002年 | 115篇 |
2001年 | 17篇 |
2000年 | 12篇 |
1999年 | 31篇 |
1998年 | 28篇 |
1997年 | 21篇 |
1996年 | 20篇 |
1995年 | 30篇 |
1994年 | 18篇 |
1993年 | 23篇 |
1992年 | 20篇 |
1991年 | 16篇 |
1990年 | 24篇 |
1989年 | 16篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 11篇 |
1981年 | 16篇 |
1980年 | 8篇 |
1979年 | 5篇 |
1978年 | 14篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1974年 | 12篇 |
1973年 | 5篇 |
排序方式: 共有2764条查询结果,搜索用时 15 毫秒
81.
Isabella Panfoli Laura Santucci Maurizio Bruschi Andrea Petretto Daniela Calzia Luca A. Ramenghi 《Expert review of proteomics》2013,10(10):801-808
ABSTRACTIntroduction: Shed by most cells, in response to a myriad of stimuli, extracellular vesicles (EVs) carry proteins, lipids, and various nucleic acids. EVs encompass diverse subpopulations differing for biogenesis and content. Among these, microvesicles (MVs) derived from plasma membrane, are key regulators of physiopathological cellular processes including cancer, inflammation and infection. This review is unique in that it focuses specifically on the MVs as a mediator of information transfer. In fact, few proteomic studies have rigorously distinguished MVs from exosomes.Areas covered: Aim of this review is to discuss the proteomic analyses of the MVs. Many studies have examined mixed populations containing both exosomes and MVs. We discuss MVs’ role in cell-specific interactions. We also show their emerging roles in therapy and diagnosis.Expert commentary: We see MVs as therapeutic tools for potential use in precision medicine. They may also have potential for allowing the identification of new biomarkers. MVs represent an invaluable tool for studying the cell of origin, which they closely represent, but it is critical to build a repository with data from MVs to deepen our understanding of their molecular repertoire and biological functions. 相似文献
82.
Francesca Suriano Emanuela Altobelli Federico Sergi Maurizio Buscarini 《Reviews in urology》2013,15(3):108-112
External beam radiotherapy (EBRT) is frequently used in the management of prostate cancer (PCa) as definitive, postoperative, or salvage local treatment. Although EBRT plays a central role in the management of PCa, complications remain a troubling by-product. Several studies have demonstrated an association between radiotherapy and elevated risk of acute and late toxicities. A secondary malignancy induced by initial therapy represents one of the most serious complications related to definitive cancer treatment. The radiation-related secondary primary malignancy risk increases with increasing survival time. Transitional cell carcinoma of the bladder is the most frequent secondary primary malignancy occurring after radiotherapy and is described as more aggressive; it may be diagnosed later because some radiation oncologists believe that the hematuria that occurs after prostate EBRT is normal. Some patients treated for localized PCa will subsequently develop invasive bladder cancer requiring surgical intervention. Patients with PCa treated with EBRT should be monitored closely for the presence of bladder cancer.Key words: Bladder cancer, Prostate cancer, Radiotherapy, External beam radiotherapyThe phenomenon of radiation-inducing the carcinogenesis has been well described in literature for decades. The correlation between ionizing radiation and DNA damage has been discussed in several studies.1–4 Most of these studies evaluated the growth of solid tumors in a large population exposed to moderate to heavy doses of radiation, such as factory workers, patients exposed to a large number of diagnostic radiographic studies, and survivors of atomic and nuclear explosions. 1 The casual effects of radiation exposure with subsequent mutagenesis are quite clear, shown both in vivo and in vitro.2 Previous radiotherapy (RT) for prostate cancer (PCa) may play an important role in the development of secondary primary bladder cancer. This is a fairly uncommon event but a very real entity, of which both urologists and radiation oncologists need to be aware. 相似文献
83.
In this contribution the results of a zoogeographical analysis, carried out on the 123 endemic leaf beetle species (Coleoptera: Chrysomelidae) occurring in Italy and its immediately adjacent regions, are reported. To assess the level of faunistic similarity among the different geographic regions studied, a cluster analysis was performed, based on the endemic component. This was done by calculating the Baroni Urbani & Buser’s similarity index (BUB). Finally, a parsimony analysis of endemicity (PAE) was used to identify the most important areas of endemism in Italy. 相似文献
84.
Richard W. Browne Michael S. Bloom Enrique F. Schisterman Kathy Hovey Maurizio Trevisan Chengqing Wu 《Biomarkers》2013,18(2):160-183
Little information is available on the intra-individual variability of oxidative stress biomarkers in healthy individuals and even less in the context of the menstrual cycle. The objective of this study was to characterize the analytical and biological variability of a panel of 21 markers of oxidative damage, antioxidant defence and micronutrients in nine healthy, regularly menstruating women aged 18–44 years. Analyses included measurement of lipid peroxidation, antioxidant enzymes and antioxidant vitamins. Blood specimens were collected, processed and stored using standardized procedures on days 2, 7, 12, 13, 14, 18, 22 and 28 in one cycle for each subject. Replicate analyses of markers were performed and two-way nested random effects ANOVA was used to describe analytical, intra-individual and inter-individual variability. No statistically significant differences at α=0.05, or temporal effects across the menstrual cycle were observed. Analytical variability was the smallest component of variance for all variables. The ICC among replicates ranged from 0.80 to 0.98. Imprecision based on quality control materials ranged from 1 to 11%. The critical differences between serial results varied greatly between assays ranging from 6 to 216% of the mean level. These results provide important initial information on the variability of biomarkers of oxidative stress, antioxidant defence and micronutrients across the menstrual cycle. 相似文献
85.
Carlo Tocchi Ermanno Federici Silvia Scargetta Alessandro D’Annibale Maurizio Petruccioli 《Process Biochemistry》2013,48(5-6):941-944
An industrial three-cascade-reactor plant treating 45 m3 d?1 of dairy wastewater (DW) was monitored for approx. one year to investigate the effect of variable daily influent loads. It removed more than 85% COD, NH4-N and non-ionic and anionic surfactants from DW within the loads 7–24, 0.4–2.3, 0.4–0.7 and 0.1–0.5 kg d?1, respectively; NH4-N removal, in particular, was almost quantitative. Although the degradation of the above parameters below the lower load thresholds declined to 78.7, 87.5, 50.2 and 64.7%, respectively, their residual concentrations met effluent discharge standards. The biomass settling properties, assessed as sludge volume index (SVI), were satisfactory (generally lower than 150 ml g?1) regardless of the organic load of the influent. The depletion of the pollutant load took mainly place in the first reactor albeit a significant contribution to the removal of the slowly degradable organic matter fraction was given by the two subsequent reactors. 相似文献
86.
87.
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88.
In this work, we explore the feasibility of regulating the collective behavior of zebrafish with a free-swimming robotic fish. The visual cues elicited by the robot are inspired by salient features of attraction in zebrafish and include enhanced coloration, aspect ratio of a fertile female, and carangiform/subcarangiform locomotion. The robot is autonomously controlled with an online multi-target tracking system and swims in circular trajectories in the presence of groups of zebrafish. We investigate the collective response of zebrafish to changes in robot speed, achieved by varying its tail-beat frequency. Our results show that the speed of the robot is a determinant of group cohesion, quantified through zebrafish nearest-neighbor distance, which increases with the speed of the robot until it reaches . We also find that the presence of the robot causes a significant decrease in the group speed, which is not accompanied by an increase in the freezing response of the subjects. Findings of this study are expected to inform the design of experimental protocols that leverage the use of robots to study the zebrafish animal model. 相似文献
89.
Jurgen Vercauteren Gertjan Beheydt Mattia Prosperi Pieter Libin Stijn Imbrechts Ricardo Camacho Bonaventura Clotet Andrea De Luca Zehava Grossman Rolf Kaiser Anders S?nnerborg Carlo Torti Eric Van Wijngaerden Jean-Claude Schmit Maurizio Zazzi Anna-Maria Geretti Anne-Mieke Vandamme Kristel Van Laethem 《PloS one》2013,8(4)
Introduction
Clinically evaluating genotypic interpretation systems is essential to provide optimal guidance in designing potent individualized HIV-regimens. This study aimed at investigating the ability of the latest Rega algorithm to predict virological response on a short and longer period.Materials & Methods
9231 treatment changes episodes were extracted from an integrated patient database. The virological response after 8, 24 and 48 weeks was dichotomized to success and failure. Success was defined as a viral load below 50 copies/ml or alternatively, a 2 log decrease from the baseline viral load at 8 weeks. The predictive ability of Rega version 8 was analysed in comparison with that of previous evaluated version Rega 5 and two other algorithms (ANRS v2011.05 and Stanford HIVdb v6.0.11). A logistic model based on the genotypic susceptibility score was used to predict virological response, and additionally, confounding factors were added to the model. Performance of the models was compared using the area under the ROC curve (AUC) and a Wilcoxon signed-rank test.Results
Per unit increase of the GSS reported by Rega 8, the odds on having a successful therapy response on week 8 increased significantly by 81% (OR = 1.81, CI = [1.76–1.86]), on week 24 by 73% (OR = 1.73, CI = [1.69–1.78]) and on week 48 by 85% (OR = 1.85, CI = [1.80–1.91]). No significant differences in AUC were found between the performance of Rega 8 and Rega 5, ANRS v2011.05 and Stanford HIVdb v6.0.11, however Rega 8 had the highest sensitivity: 76.9%, 76.5% and 77.2% on 8, 24 and 48 weeks respectively. Inclusion of additional factors increased the performance significantly.Conclusion
Rega 8 is a significant predictor for virological response with a better sensitivity than previously, and with rules for recently approved drugs. Additional variables should be taken into account to ensure an effective regimen. 相似文献90.
Giovanna Poce Robert H. Bates Salvatore Alfonso Martina Cocozza Giulio Cesare Porretta Lluís Ballell Joaquin Rullas Fátima Ortega Alessandro De Logu Emanuela Agus Valentina La Rosa Maria Rosalia Pasca Edda De Rossi Baojie Wae Scott G. Franzblau Fabrizio Manetti Maurizio Botta Mariangela Biava 《PloS one》2013,8(2)
1,5-Diphenyl pyrroles were previously identified as a class of compounds endowed with high in vitro efficacy against M. tuberculosis. To improve the physical chemical properties and drug-like parameters of this class of compounds, a medicinal chemistry effort was undertaken. By selecting the optimal substitution patterns for the phenyl rings at N1 and C5 and by replacing the thiomorpholine moiety with a morpholine one, a new series of compounds was produced. The replacement of the sulfur with oxygen gave compounds with lower lipophilicity and improved in
vitro microsomal stability. Moreover, since the parent compound of this family has been shown to target MmpL3, mycobacterial mutants resistant to two compounds have been isolated and characterized by sequencing the mmpL3 gene; all the mutants showed point mutations in this gene. The best compound identified to date was progressed to dose-response studies in an acute murine TB infection model. The resulting ED99 of 49 mg/Kg is within the range of commonly employed tuberculosis drugs, demonstrating the potential of this chemical series. The in vitro and in vivo target validation evidence presented here adds further weight to MmpL3 as a druggable target of interest for anti-tubercular drug discovery. 相似文献