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81.
The leader gene approach is a data mining method based on the systematic search for genes involved in a specific process and their ranking according to the number of interconnections with the other genes identified. The genes with the strongest interconnections are termed leader genes, since they may be supposed to play an important role in the process. The potential of malignant progression of OLP to oral squamous cell carcinoma (OSCC) is still not completely clear. In this study, the leader gene approach is applied to investigate the association between OLP and OSCC at a molecular level. Results were integrated with those obtained in an experimental analysis (see paper 1 of this series). Genes involved in OLP and OSCC were identified by systematic queries to dedicated databases. Interconnections among identified genes were calculated and given a confidence value using STRING database. Leader genes were identified by clustering genes according to their interconnections. This theoretical analysis shows that OLP and OSCC share two leader genes: TP53 and CDKN1A, involved in the PI3K signalling events mediated by AKT pathway. This finding and those obtained in the experimental analysis suggest the possible involvement of some key genes/proteins LCK, PIK3CA, BIRC5, TP53 and CDKN1A in the malignant progression from OLP to OSCC. Moreover, these findings support the role of some molecular pathways, namely IL2 signalling events mediated by PI3K, PI3K signalling events mediated by AKT, and, possibly, Aurora A signalling in the association between OLP and OSCC. 相似文献
82.
Maddalena Rossi Pietro Buzzini Lisa Cordisco Alberto Amaretti Maurizio Sala Stefano Raimondi Chiara Ponzoni Ugo Maria Pagnoni & Diego Matteuzzi 《FEMS microbiology ecology》2009,69(3):363-372
Obligate psychrophilic, facultative psychrophilic, and mesophilic yeasts were cultured in a carbon-rich medium at different temperatures to investigate whether growth parameters, lipid accumulation, and fatty acid (FA) composition were adaptive and/or acclimatory responses. Acclimation of facultative psychrophiles and mesophiles to a lower temperature decreased their specific growth rate, but did not affect their biomass yield (YX/S ). Obligate and facultative psychrophiles exhibited the highest YX/S . Acclimation to lower temperature decreased the lipid yield (YL/X ) in mesophilic yeasts, but did not affect YL/X in facultative psychrophilic ones. Similar YL/X were found in both groups of psychrophiles, suggesting that lipid accumulation is not a distinctive characteristic of adaptation to permanently cold environments. The unsaturation of FAs was one major adaptive feature of the yeasts colonizing permanently cold ecosystems. Remarkable amounts of α-linolenic acid were found in obligate psychrophiles at the expense of linoleic acid, whereas it was scarce or absent in all the other strains. Increased unsaturation of FAs was also a general acclimatory response of facultative psychrophiles to a lower temperature. These results improve the knowledge of the responses enabling psychrophilic yeasts to cope with the cold and may be of support for potential biotechnological exploitation of these strains. 相似文献
83.
84.
Maria Pala Anna Olivieri Ugo A. Perego Daria Sanna Kristiina Tambets Matteo Accetturo Hovirag Lancioni Bettina Zimmermann Nadia Al-Zahery Francesca Brisighelli Paolo Francalacci Antonio Salas Richard Villems Hans-Jürgen Bandelt 《American journal of human genetics》2009,84(6):814-821
There are extensive data indicating that some glacial refuge zones of southern Europe (Franco-Cantabria, Balkans, and Ukraine) were major genetic sources for the human recolonization of the continent at the beginning of the Holocene. Intriguingly, there is no genetic evidence that the refuge area located in the Italian Peninsula contributed to this process. Here we show, through phylogeographic analyses of mitochondrial DNA (mtDNA) variation performed at the highest level of molecular resolution (52 entire mitochondrial genomes), that the most likely homeland for U5b3—a haplogroup present at a very low frequency across Europe—was the Italian Peninsula. In contrast to mtDNA haplogroups that expanded from other refugia, the Holocene expansion of haplogroup U5b3 toward the North was restricted by the Alps and occurred only along the Mediterranean coasts, mainly toward nearby Provence (southern France). From there, ∼7,000–9,000 years ago, a subclade of this haplogroup moved to Sardinia, possibly as a result of the obsidian trade that linked the two regions, leaving a distinctive signature in the modern people of the island. This scenario strikingly matches the age, distribution, and postulated geographic source of a Sardinian Y chromosome haplogroup (I2a2-M26), a paradigmatic case in the European context of a founder event marking both female and male lineages. 相似文献
85.
Ugo Bonfanti Domenica Lamparelli Paolo Colombo & Claudio Bernardi 《Journal of medical primatology》2009,38(4):228-235
Background The vast majority of non-human primates used for experimental activities are purpose-bred. However, in case of particular procedures or specific projects, it may still be necessary to use animals captured in the wild.
Methods Sixty cynomolgus monkeys were randomly selected on the basis of breeding origin, and assigned to two groups, each of fifteen males and fifteen females. Analyses included the most frequently investigated parameters for hematology, coagulation, and biochemistry.
Results Differences were observed in some parameters, particularly in eosinophils, basophils and monocytes, and in fibrinogen, total protein, globulins, alanine amino-transferase, creatinine, aspartate amino-transferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, iron, potassium, and phosphorus.
Conclusions Some values in the cynomolgus monkey may show significant differences according to the breeding background of the animals. Only data obtained from animals of similar origin have to be compared, to avoid misinterpretation during the evaluation of the experimental results. 相似文献
Methods Sixty cynomolgus monkeys were randomly selected on the basis of breeding origin, and assigned to two groups, each of fifteen males and fifteen females. Analyses included the most frequently investigated parameters for hematology, coagulation, and biochemistry.
Results Differences were observed in some parameters, particularly in eosinophils, basophils and monocytes, and in fibrinogen, total protein, globulins, alanine amino-transferase, creatinine, aspartate amino-transferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, iron, potassium, and phosphorus.
Conclusions Some values in the cynomolgus monkey may show significant differences according to the breeding background of the animals. Only data obtained from animals of similar origin have to be compared, to avoid misinterpretation during the evaluation of the experimental results. 相似文献
86.
Tarantino U Capone A Planta M D'Arienzo M Letizia Mauro G Impagliazzo A Formica A Pallotta F Patella V Spinarelli A Pazzaglia U Zarattini G Roselli M Montanari G Sessa G Privitera M Verdoia C Corradini C Feola M Padolino A Saturnino L Scialdoni A Rao C Iolascon G Brandi ML Piscitelli P 《Arthritis research & therapy》2010,12(6):R226-9
Introduction
We aimed to assess the incidence and hospitalization rate of hip and "minor" fragility fractures in the Italian population.Methods
We carried out a 3-year survey at 10 major Italian emergency departments to evaluate the hospitalization rate of hip, forearm, humeral, ankle, and vertebral fragility fractures in people 45 years or older between 2004 and 2006, both men and women. These data were compared with those recorded in the national hospitalizations database (SDO) to assess the overall incidence of fragility fractures occurring at hip and other sites, including also those events not resulting in hospital admissions.Results
We observed 29,017 fractures across 3 years, with hospitalization rates of 93.0% for hip fractures, 36.3% for humeral fractures, 31.3% for ankle fractures, 22.6% for forearm/wrist fractures, and 27.6% for clinical vertebral fractures. According to the analyses performed with the Italian hospitalization database in year 2006, we estimated an annual incidence of 87,000 hip, 48,000 humeral, 36,000 ankle, 85,000 wrist, and 155,000 vertebral fragility fractures in people aged 45 years or older (thus resulting in almost 410,000 new fractures per year). Clinical vertebral fractures were recorded in 47,000 events per year.Conclusions
The burden of fragility fractures in the Italian population is very high and calls for effective preventive strategies. 相似文献87.
88.
Alessia Calzolari Luigi Maria Larocca Silvia Deaglio Veronica Finisguerra Alessandra Boe Carla Raggi Lucia Ricci-Vitani Francesco Pierconti Fabio Malavasi Ruggero De Maria Ugo Testa Roberto Pallini 《Translational oncology》2010,3(2):123-134
Under physiological conditions, transferrin receptor 2 (TfR2) is expressed in the liver and its balance is related to the cell cycle rather than to intracellular iron levels. We recently showed that TfR2 is highly expressed in glioblastoma cell lines. Here, we demonstrate that, in these cells, TfR2 appears to localize in lipid rafts, induces extracellular signal-regulated kinase 1/2 phosphorylation after transferrin binding, and contributes to cell proliferation, as shown by RNA silencing experiments. In vitro hypoxic conditions induce a significant TfR2 up-regulation, suggesting a role in tumor angiogenesis. As assessed by immunohistochemistry, the level of TfR2 expression in astrocytic tumors is related to histologic grade, with the highest expression observed in glioblastomas. The level of TfR2 expression represents a favorable prognostic factor, which is associated with the higher sensitivity to temozolomide of TfR2-positive tumor cells in vitro. The endothelial cells of glioblastoma vasculature also stain for TfR2, whereas those of the normal brain vessels do not. Importantly, TfR2 is expressed by the subpopulation of glioblastoma cells with properties of cancer-initiating cells. TfR2-positive glioblastoma cells retain their TfR2 expression on xenografting in immunodeficient mice. In conclusion, our observations demonstrate that TfR2 is a neoantigen for astrocytomas that seems attractive for developing target therapies. 相似文献
89.
Neutral evolution is the simplest model of molecular evolution and thus it is most amenable to a comprehensive theoretical investigation. In this paper, we characterize the statistical properties of neutral evolution of proteins under the requirement that the native state remains thermodynamically stable, and compare them to the ones of Kimura's model of neutral evolution. Our study is based on the Structurally Constrained Neutral (SCN) model which we recently proposed. We show that, in the SCN model, the substitution rate decreases as longer time intervals are considered. Fluctuations from one branch of the evolutionary tree to another are strong, leading to a non-Poissonian statistics for the substitution process. Such strong fluctuations are in part due to the fact that neutral substitution rates for individual residues are strongly correlated for most residue pairs. Interestingly, structurally conserved residues, characterized by a much below average substitution rate, are also much less correlated to other residues and evolve in a much more regular way. Our results can improve methods aimed at distinguishing between neutral and adaptive substitutions as well as methods for computing the expected number of substitutions occurred since the divergence of two protein sequences. In particular, we compute the minimal sequence similarity below which no information about the evolutionary divergence of the compared sequences can be obtained. 相似文献
90.
Bastolla U Porto M Eduardo Roman MH Vendruscolo MH 《Journal of molecular evolution》2003,56(3):243-254
Abstract
Protein structures are much more conserved than sequences during evolution. Based on this observation, we investigate the
consequences of structural conservation on protein evolution. We study seven of the most studied protein folds, determining
that an extended neutral network in sequence space is associated with each of them. Within our model, neutral evolution leads
to a non-Poissonian substitution process, due to the broad distribution of connectivities in neutral networks. The observation
that the substitution process has non-Poissonian statistics has been used to argue against the original Kimura neutral theory,
while our model shows that this is a generic property of neutral evolution with structural conservation. Our model also predicts
that the substitution rate can strongly fluctuate from one branch to another of the evolutionary tree. The average sequence
similarity within a neutral network is close to the threshold of randomness, as observed for families of sequences sharing
the same fold. Nevertheless, some positions are more difficult to mutate than others. We compare such structurally conserved
positions to positions conserved in protein evolution, suggesting that our model can be a valuable tool to distinguish structural
from functional conservation in databases of protein families. These results indicate that a synergy between database analysis
and structurally based computational studies can increase our understanding of protein evolution. 相似文献