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51.
Ohne ZusammenfassungMit 8 Textabbildungen. 相似文献
52.
Carolina Souza Gusatti Cintia Costi Maria Laura Halon Tarciana Grandi Arlete Ferrari Rech Medeiros Cláudia Maria Dornelles Silva Selma Andrade Gomes Marcia Susana Nunes Silva Christian Niel Maria Lucia Rosa Rossetti 《PloS one》2015,10(8)
Hepatitis B virus genotype A1 (HBV/A1), of African origin, is the most prevalent genotype in Brazil, while HBV/F predominates in the other South American countries. However, HBV/D is the most common in the three states of southern Brazil, where ‘islands’ of elevated prevalence, as Chapecó and other cities, have been described. In this study, 202 HBV chronic carriers attending in 2013 the viral hepatitis ambulatory of Chapecó, were investigated. In comparison with previous studies performed in the same ambulatory, a rapid aging of the HBV infected population was observed (mean age of the newly diagnosed patients increasing from 29.9 ± 10.3 years in 1996 to 44.4 ± 13.3 years in 2013), probably due to a singular vaccination schedule at Chapecó that included not only children but also adolescents. Phylogenetic and BLAST analyses (S region) classified 91 HBV isolates into genotypes A (n = 3) and D (n = 88). The majority of HBV/D isolates were closely related to D3 sequences. To understand the reasons for the absence or near absence of genotypes A and F, and how HBV/D was introduced in the south of Brazil, HBV/D infected patients were inquired about their genealogical and geographical origins. Forty-three (52%) patients have their four grandparents of Italian origin, vs. seven (8%) who have their four grandparents of Brazilian origin. At all, 65 out of 83 (78%) patients had at least one grandparent originating from Italy. Taking into consideration the fact that Italy is one of the few countries where subgenotype D3 is predominant, the results strongly suggested that HBV/D was introduced in Brazil through Italian immigration which culminated between 1870 and 1920. 相似文献
53.
Yimer Wasihun Kifle Nele Goeyvaerts Kim Van Kerckhove Lander Willem Christel Faes Herwig Leirs Niel Hens Philippe Beutels 《PloS one》2015,10(7)
Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0–9 years) and adults (25–54 years) have the highest potential to cause a major zoonotic outbreak. 相似文献
54.
Lander Willem Sean Stijven Ekaterina Vladislavleva Jan Broeckhove Philippe Beutels Niel Hens 《PLoS computational biology》2014,10(4)
Modeling plays a major role in policy making, especially for infectious disease interventions but such models can be complex and computationally intensive. A more systematic exploration is needed to gain a thorough systems understanding. We present an active learning approach based on machine learning techniques as iterative surrogate modeling and model-guided experimentation to systematically analyze both common and edge manifestations of complex model runs. Symbolic regression is used for nonlinear response surface modeling with automatic feature selection. First, we illustrate our approach using an individual-based model for influenza vaccination. After optimizing the parameter space, we observe an inverse relationship between vaccination coverage and cumulative attack rate reinforced by herd immunity. Second, we demonstrate the use of surrogate modeling techniques on input-response data from a deterministic dynamic model, which was designed to explore the cost-effectiveness of varicella-zoster virus vaccination. We use symbolic regression to handle high dimensionality and correlated inputs and to identify the most influential variables. Provided insight is used to focus research, reduce dimensionality and decrease decision uncertainty. We conclude that active learning is needed to fully understand complex systems behavior. Surrogate models can be readily explored at no computational expense, and can also be used as emulator to improve rapid policy making in various settings. 相似文献
55.
Frederic Cedrone Sebastien Niel Sanja Roca Tej Bhatnagar Nadra Ait-abdelkader Claudia Torre 《Biocatalysis and Biotransformation》2013,31(6):357-364
An efficient and genetically stable expression system for the directed evolution of epoxide hydrolase from Aspergillus niger (ANEH) has been constructed. Error prone polymerase chain reaction (PCR) with defined mutation rates was used to create biodiversity in two libraries of mutants. Screening for activity allowed the isolation of clones with improved properties. One of these clones shows an expression level 3.4 higher than the original wild type clone in E.?coli SG13009 and a 3.3 fold increased catalytic efficiency on 4-(p-nitrophenoxy)-1,2-epoxybutane. In addition, a screening assay for determining the enantioselectivity in the kinetic resolution of styrene oxide has been established using mass spectrometry. 相似文献
56.
Verschoor CP Pant SD Biggar GA Schenkel FS Sharma BS Karrow NA 《Animal biotechnology》2011,22(1):7-15
Genetic variants in a number of immunoregulatory genes have been previously associated with health and production traits in dairy cattle. Therefore, in the following study, the genes coding interferon gamma (IFNG), IFNG receptor 1 and 2 domains, interleukin-22 (IL22), and IL22 receptor alpha 1, were investigated for single nucleotide polymorphisms (SNPs) in Holstein bulls. These SNPs, along with SNPs previously identified in IL10, IL10 receptor, and transforming growth factor beta 1 (TGFB1) genes, were evaluated for statistical associations to estimated breeding values for milk somatic cell score (SCS), a trait highly correlated to mastitis incidence, and various production-related traits, including milk yield, protein yield, fat yield, and lactation persistency. While no significant associations were found between these SNPs and SCS, SNPs in IL10 receptor beta subunit showed a significant effect on protein yield and lactation persistency. While there is evidence that IL10 plays an important role during lactation, it is also likely that the effects of SNPs in IL10 receptor beta subunit on protein yield and lactation persistency are due to linkage disequilibrium with a neighboring QTL. 相似文献
57.
Horby P Pham QT Hens N Nguyen TT Le QM Dang DT Nguyen ML Nguyen TH Alexander N Edmunds WJ Tran ND Fox A Nguyen TH 《PloS one》2011,6(2):e16965
Background
The spread of infectious diseases from person to person is determined by the frequency and nature of contacts between infected and susceptible members of the population. Although there is a long history of using mathematical models to understand these transmission dynamics, there are still remarkably little empirical data on contact behaviors with which to parameterize these models. Even starker is the almost complete absence of data from developing countries. We sought to address this knowledge gap by conducting a household based social contact diary in rural Vietnam.Methods and Findings
A diary based survey of social contact patterns was conducted in a household-structured community cohort in North Vietnam in 2007. We used generalized estimating equations to model the number of contacts while taking into account the household sampling design, and used weighting to balance the household size and age distribution towards the Vietnamese population. We recorded 6675 contacts from 865 participants in 264 different households and found that mixing patterns were assortative by age but were more homogenous than observed in a recent European study. We also observed that physical contacts were more concentrated in the home setting in Vietnam than in Europe but the overall level of physical contact was lower. A model of individual versus household vaccination strategies revealed no difference between strategies in the impact on R 0.Conclusions and Significance
This work is the first to estimate contact patterns relevant to the spread of infections transmitted from person to person by non-sexual routes in a developing country setting. The results show interesting similarities and differences from European data and demonstrate the importance of context specific data. 相似文献58.
Elena Odintsova Guillaume van Niel Hélène Conjeaud Gra?a Raposo Ryo Iwamoto Eisuke Mekada Fedor Berditchevski 《The Journal of biological chemistry》2013,288(36):26323-26334
Ligand-induced ubiquitylation of EGF receptor (EGFR) is an important regulatory mechanism that controls endocytic trafficking of the receptor and its signaling potential. Here we report that tetraspanin CD82/KAI1 specifically suppresses ubiquitylation of EGFR after stimulation with heparin-binding EGF or amphiregulin and alters the rate of recruitment of the activated receptor to EEA1-positive endosomes. The suppressive effect of CD82 is dependent on the heparin-binding domain of the ligand. Deletion of the C-terminal cytoplasmic domain of CD82 (CD82ΔC mutant) inhibits endocytic trafficking of the tetraspanin and compromises its activity toward heparin-binding EGF-activated EGFR. Reduced ubiquitylation of EGFR is accompanied by PKC-dependent increase in serine phosphorylation of c-Cbl in cells expressing elevated levels of CD82. Furthermore, phosphorylation of threonine 654 (PKC phosphorylation site) in the juxtamembrane domain of the receptor is considerably increased in CD82-expressing cells. These results describe previously unsuspected links between tetraspanin proteins and ubiquitylation of their molecular partners (e.g., EGFR). Our data identify CD82 as a new regulator of c-Cbl, which discriminatively controls the activity of this E3 ubiquitin ligase toward heparin-binding ligand-EGFR pairs. Taken together, these observations provide an important new insight into the modulatory role of CD82 in endocytic trafficking of EGF receptor. 相似文献
59.
Tarciana Grandi Cláudia Maria Dornelles da Silva Karine Medeiros Amaral Paulo Dornelles Picon Cintia Costi Nicole Nascimento da Fré Marilu Fiegenbaum Christian Niel Maria Lucia Rosa Rossetti 《Memórias do Instituto Oswaldo Cruz》2013,108(1):48-53
A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis. 相似文献
60.
Brenda Watt Guillaume van Niel Graça Raposo Michael S. Marks 《Pigment cell & melanoma research》2013,26(3):300-315
PMEL is a pigment cell‐specific protein responsible for the formation of fibrillar sheets within the pigment organelle, the melanosome. The fibrillar sheets serve as a template upon which melanins polymerize as they are synthesized. The PMEL fibrils are required for optimal pigment cell function, as animals that either lack PMEL expression or express mutant PMEL variants show varying degrees of hypopigmentation and pigment cell inviability. The PMEL fibrils have biophysical properties of amyloid, a protein fold that is frequently associated with neurodegenerative and other diseases. However, PMEL is one of a growing number of non‐pathogenic amyloid proteins that contribute to the function of the cell and/or organism that produces them. Understanding how PMEL generates amyloid in a non‐pathogenic manner might provide insights into how to avoid toxicity due to pathological amyloid formation. In this review, we summarize and reconcile data concerning the fate of PMEL from its site of synthesis in the endoplasmic reticulum to newly formed melanosomes and the role of distinct PMEL subdomains in trafficking and amyloid fibril formation. We then discuss how its progression through the secretory pathway into the endosomal system might allow for the regulated and non‐toxic conversion of PMEL into an ordered amyloid polymer. 相似文献