全文获取类型
收费全文 | 489篇 |
免费 | 43篇 |
专业分类
532篇 |
出版年
2023年 | 3篇 |
2022年 | 12篇 |
2021年 | 15篇 |
2020年 | 15篇 |
2019年 | 17篇 |
2018年 | 23篇 |
2017年 | 7篇 |
2016年 | 20篇 |
2015年 | 32篇 |
2014年 | 28篇 |
2013年 | 41篇 |
2012年 | 34篇 |
2011年 | 24篇 |
2010年 | 25篇 |
2009年 | 18篇 |
2008年 | 15篇 |
2007年 | 23篇 |
2006年 | 22篇 |
2005年 | 16篇 |
2004年 | 19篇 |
2003年 | 20篇 |
2002年 | 12篇 |
2001年 | 7篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 9篇 |
1997年 | 10篇 |
1996年 | 9篇 |
1995年 | 9篇 |
1994年 | 4篇 |
1993年 | 8篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1974年 | 1篇 |
排序方式: 共有532条查询结果,搜索用时 0 毫秒
11.
Drumo R Widmer G Morrison LJ Tait A Grelloni V D'Avino N Pozio E Cacciò SM 《Applied and environmental microbiology》2012,78(10):3523-3529
Recent studies have revealed extensive genetic variation among isolates of Cryptosporidium parvum, an Apicomplexan parasite that causes gastroenteritis in both humans and animals worldwide. The parasite's population structure is influenced by the intensity of transmission, the host-parasite interaction, and husbandry practices. As a result, C. parvum populations can be panmictic, clonal, or even epidemic on both a local scale and a larger geographical scale. To extend the study of C. parvum populations to an unexplored region, 173 isolates of C. parvum collected in Italy from humans and livestock (calf, sheep, and goat) over a 10-year period were genotyped using a multilocus scheme based on 7 mini- and microsatellite loci. In agreement with other studies, extensive polymorphism was observed, with 102 distinct multilocus genotypes (MLGs) identified among 173 isolates. The presence of linkage disequilibrium, the confinement of MLGs to individual farms, and the relationship of many MLGs inferred using network analysis (eBURST) suggest a predominantly clonal population structure, but there is also evidence that part of the diversity can be explained by genetic exchange. MLGs from goats were found to differ from bovine and sheep MLGs, supporting the existence of C. parvum subpopulations. Finally, MLGs from isolates collected between 1997 and 1999 were also identified as a distinct subgroup in principal-component analysis and eBURST analysis, suggesting a continuous introduction of novel genotypes in the parasite population. 相似文献
12.
Edoardo Saccenti Age K. Smilde José Camacho 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):73
Introduction
Modern omics experiments pertain not only to the measurement of many variables but also follow complex experimental designs where many factors are manipulated at the same time. This data can be conveniently analyzed using multivariate tools like ANOVA-simultaneous component analysis (ASCA) which allows interpretation of the variation induced by the different factors in a principal component analysis fashion. However, while in general only a subset of the measured variables may be related to the problem studied, all variables contribute to the final model and this may hamper interpretation.Objectives
We introduce here a sparse implementation of ASCA termed group-wise ANOVA-simultaneous component analysis (GASCA) with the aim of obtaining models that are easier to interpret.Methods
GASCA is based on the concept of group-wise sparsity introduced in group-wise principal components analysis where structure to impose sparsity is defined in terms of groups of correlated variables found in the correlation matrices calculated from the effect matrices.Results
The GASCA model, containing only selected subsets of the original variables, is easier to interpret and describes relevant biological processes.Conclusions
GASCA is applicable to any kind of omics data obtained through designed experiments such as, but not limited to, metabolomic, proteomic and gene expression data.13.
A Moretto F Formaggio M Crisma C Toniolo M Saviano R Iacovino R M Vitale E Benedetti 《The journal of peptide research》2001,57(4):307-315
Two complete series of N-protected oligopeptide esters to the pentamer level from 1-amino-cyclodecane-1-carboxylic acid (Ac10c), an alpha-amino acid conformationally constrained through a medium-ring Calphai <--> Calphai cyclization, and either the L-Ala or Aib residue, along with the N-protected Ac10c monomer and homo-dimer alkylamides, were synthesized using solution methods and fully characterized. The preferred conformation of these model peptides was assessed in deuterochloroform solution using FT-IR absorption and 1H NMR techniques. Furthermore, the molecular structures of two derivatives (Z-Ac10c-OH and Fmoc-Ac10c-OH) and two peptides (the dipeptide ester Z-Ac10c-L-Phe-OMe and the tripeptide ester Z-Aib-Ac10c-Aib-OtBu) were determined in the crystal state using X-ray diffraction. The experimental results support the view that beta-bends and 3(10)-helices are preferentially adopted by peptides rich in Ac10c, the third largest cycloaliphatic C(alpha,alpha)-disubstituted glycine known. This investigation allowed us to complete a detailed conformational analysis of the whole 1-amino-cycloalkane-1-carboxylic acid (Ac(n)c, with n = 3-12) series, which represents the prerequisite for our recent proposal of the 'Ac(n)c scan' concept. 相似文献
14.
Global stability of an SIR epidemic model with time delays 总被引:11,自引:0,他引:11
An SIR disease transmission model is formulated under the assumption that the force of infection at the present time depends on the number of infectives at the past. It is shown that a disease free equilibrium point is globally stable if no endemic equilibrium point exists. Further the endemic point (if it exists) is globally stable with respect to the whole state space except the neighborhood of the disease free state.Research partly supported by the Ministry of Education, Science and Culture, Japan, Grant 05640256 相似文献
15.
Lorenzo Andreani Edoardo Ipponi Damiano Alfio Ruinato Silvia De Franco Antonio DArienzo Rodolfo Capanna 《Journal of musculoskeletal & neuronal interactions》2022,22(1):87
Objectives:Peroneal nerves Schwannomas are rare benign tumors. Literature is still poor of studies about clinical and functional outcomes after surgical treatment. We evaluated the pre-operative presentation of the disease and assessed clinical and functional outcomes after surgery.Methods:We collected all the cases of peroneal nerves’ neurinoma treated surgically between June 2016 and June 2020. We analyzed each patients’ personal data and carried out accurate clinical examinations before and after surgery. MRI was performed both pre-operatively and post-operatively.Results:We reported 9 cases of peroneal nerves schwannomas: five arising from the common peroneal nerve and four arising from the deep or superficial branches alone. Their mean size was 22.6 mm. Each patient showed sensation deficits before surgery; pre-operative MRC score was 4.2. Pre-Operative MSTS and LEFS scores were 23.6 and 64.4. Surgery was successful in each case. No local recurrence nor major complication occurred. Tumor size was significantly associated with both diagnostic delay and development of pre-operative deficits. Surgery was proven to be globally successful: post-operative evaluations highlighted a marked reduction of neurological signs and overall functional limitations.Conclusions:Surgical treatment at early stages of the disease represents a reliable and relatively safe therapeutic option. 相似文献
16.
Alessandra Nicoletti Elisa Bruno Martina Nania Edoardo Cicero Silvia Messina Clara Chisari Josita Torrisi Davide Maimone Roberto Marziolo Salvatore Lo Fermo Francesco Patti Salvatore Giammanco Mario Zappia 《PloS one》2013,8(12)
Background
Trace elements have been hypothesised to be involved in the pathogenesis of Multiple Sclerosis and volcanic degassing is the major natural sources of trace elements. Both incidence of Multiple Sclerosis in Catania and volcanic activity of Mount Etna have been significantly increased during the last 30 years. Due to prevailing trade winds direction, volcanic gases from Etna summit craters are mostly blown towards the eastern and southern sectors of the volcano.Objective
To evaluate the possible association between Multiple Sclerosis and exposure to volcanogenic trace elements.Methods
We evaluated prevalence and incidence of Multiple Sclerosis in four communities (47,234 inhabitants) located in the eastern flank and in two communities (52,210 inhabitants) located in the western flank of Mount Etna, respectively the most and least exposed area to crater gas emissions.Results
A higher prevalence was found in the population of the eastern flank compared to the population of the western one (137.6/100,000 versus 94.3/100,000; p-value 0.04). We found a borderline significantly higher incidence risk during the incidence study period (1980–2009) in the population of the eastern flank 4.6/100,000 (95% CI 3.1–5.9), compared with the western population 3.2/100,000 (95% CI 2.4–4.2) with a RR of 1.41 (95% CI 0.97–2.05; p-value 0.06). Incidence risks have increased over the time in both populations reaching a peak of 6.4/100,000 in the eastern flank and of 4.4/100.000 in the western flank during 2000–2009.Conclusion
We found a higher prevalence and incidence of Multiple Sclerosis among populations living in the eastern flank of Mount Etna. According to our data a possible role of TE cannot be ruled out as possible co-factor in the MS pathogenesis. However larger epidemiological study are needed to confirm this hypothesis. 相似文献17.
New insights on the sialidase protein family revealed by a phylogenetic analysis in metazoa 总被引:1,自引:0,他引:1
Sialidases are glycohydrolytic enzymes present from virus to mammals that remove sialic acid from oligosaccharide chains. Four different sialidase forms are known in vertebrates: the lysosomal NEU1, the cytosolic NEU2 and the membrane-associated NEU3 and NEU4. These enzymes modulate the cell sialic acid content and are involved in several cellular processes and pathological conditions. Molecular defects in NEU1 are responsible for sialidosis, an inherited disease characterized by lysosomal storage disorder and neurodegeneration. The studies on the biology of sialic acids and sialyltransferases, the anabolic counterparts of sialidases, have revealed a complex picture with more than 50 sialic acid variants selectively present in the different branches of the tree of life. The gain/loss of specific sialoconjugates have been proposed as key events in the evolution of deuterostomes and Homo sapiens, as well as in the host-pathogen interactions. To date, less attention has been paid to the evolution of sialidases. Thus we have conducted a survey on the state of the sialidase family in metazoan. Using an in silico approach, we identified and characterized sialidase orthologs from 21 different organisms distributed among the evolutionary tree: Metazoa relative (Monosiga brevicollis), early Deuterostomia, precursor of Chordata and Vertebrata (teleost fishes, amphibians, reptiles, avians and early and recent mammals). We were able to reconstruct the evolution of the sialidase protein family from the ancestral sialidase NEU1 and identify a new form of the enzyme, NEU5, representing an intermediate step in the evolution leading to the modern NEU3, NEU4 and NEU2. Our study provides new insights on the mechanisms that shaped the substrate specificity and other peculiar properties of the modern mammalian sialidases. Moreover, we further confirm findings on the catalytic residues and identified enzyme loop portions that behave as rapidly diverging regions and may be involved in the evolution of specific properties of sialidases. 相似文献
18.
Tiberio L Tiberio GA Bardella L Cervi E Cerea K Dreano M Garotta G Fra A Montani N Ferrari-Bravo A Callea F Grigolato P Giulini SM Schiaffonati L 《Cytokine》2006,34(3-4):131-142
Numerous animal studies simulating liver injury have demonstrated that interleukin-6 (IL-6) exerts a protective effect. This study was designed to further analyze the molecular mechanisms underlying the protective role of IL-6 in a rat model of liver ischemia/reperfusion injury. We show that IL-6: (i) at high doses reduces cell damage which occurs in ischemic-reperfused liver, while at low doses displays only a limited protective capacity, (ii) anticipates and enhances hepatocyte compensatory proliferation seen in ischemic-reperfused liver also at a low, more pharmacologically acceptable dose, (iii) sustains the acute phase response which is dampened in ischemic-reperfused liver, (iv) strengthens the heat shock-stress response shown by ischemic-reperfused liver and (v) overcomes the dysfunctions of the unfolding protein response found in ischemic-reperfused liver. We also show that IL-6-enhanced STAT3 activation probably plays a crucial role in the potentiation of the different protective pathways activated in ischemic-reperfused liver. Our data confirm that IL-6 is a potential therapeutic in liver injury of different etiologies and reveal novel mechanisms by which IL-6 sustains liver function after ischemia/reperfusion injury. 相似文献
19.
Handedness preference and switching of peptide helices. Part I: Helices based on protein amino acids
Marta De Zotti Fernando Formaggio Marco Crisma Cristina Peggion Alessandro Moretto Claudio Toniolo 《Journal of peptide science》2014,20(5):307-322
In this article, we review the relevant results obtained during almost 60 years of research on a specific aspect of stereochemistry, namely handedness preference and switches between right‐handed and left‐handed helical peptide structures generated by protein amino acids or appropriately designed, side‐chain modified analogs. In particular, we present and discuss here experimental and theoretical data on three categories of those screw‐sense issues: (i) right‐handed/left‐handed α‐helix transitions underwent by peptides rich in Asp, specific Asp β‐esters, and Asn; (ii) comparison of the preferred conformations adopted by helical host–guest peptide series, each characterized by an amino acid residue (e.g. Ile or its diastereomer aIle) endowed with two chiral centers in its chemical structure; and (iii) right‐handed (type I)/left‐handed (type II) poly‐(Pro)n helix transitions monitored for peptides rich in Pro itself or its analogs with a pyrrolidine ring substitution, particularly at the biologically important position 4. The unique modular and chiral properties of peptides, combined with their relatively easy synthesis, the chance to shape them into the desired conformation, and the enormous chemical diversity of their coded and non‐coded α‐amino acid building blocks, offer a huge opportunity to structural chemists for applications to bioscience and nanoscience problems. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
20.
Carlo Andreoli Claudio Tolomio Laura Scarabel Isabella Moro Sabrina Bellato Marta Moretto 《Plant biosystems》2013,147(6):1007-1027
Abstract During research directed towards the employment of the biological resources of the North Adriatic lagoons, from January 1991 to December 1992, in both tidal phases, a survey was carried out on the phytoplankton and the chemico-physical parameters of the Scardovari lagoon. Data analyses allowed two different areas to be distinguished: one inner, which was generally characterized by high phytoplanktonic densities (St. 3–4), the other outer, which was more influced by marine load (St. 1–2). Photosynthetic picoplankton was dominant in terms of cell number in most samples. Phytoplanktonic fraction >2 μm was represented mainly by diatoms, which showed the higher species number. During the sample observation, some dinoflagellates, considered toxic or potentially toxic, were found. Their presence was important because of their effect on the bivalve mollusc cultures. 相似文献