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排序方式: 共有252条查询结果,搜索用时 15 毫秒
51.
Alessandra Bitto Natasha Irrera Gabriele Pizzino Giovanni Pallio Federica Mannino Mario Vaccaro Vincenzo Arcoraci Federica Aliquò Letteria Minutoli Michele R. Colonna Maria Rosaria Galeano Michael Brines Chiara De Ponte Massimo Collino Francesco Squadrito Domenica Altavilla 《生物化学与生物物理学报:疾病的分子基础》2018,1864(2):632-639
Diabetes is characterized by poor wound healing which currently lacks an efficacious treatment. The innate repair receptor (IRR) is a master regulator of tissue protection and repair which is expressed as a response injury or metabolic stress, including in diabetes. Activation of the IRR might provide benefit for diabetic wound healing. A specific IRR agonist cibinetide was administered in an incisional wound healing model performed mice with genetic diabetes (db+/db+) and compared to the normal wild-type. Animals were treated daily with cibinetide (30 μg/kg/s.c.) or vehicle and euthanized 3, 7, and 14 days after the injury to quantitate vascular endothelial growth factor (VEGF), malondialdehyde (MAL), phospho-Akt (pAkt), phospho e-NOS (p-eNOS), and nitrite/nitrate content within the wound. Additional evaluations included quantification of skin histological change, angiogenesis, scar strength, and time to complete wound closure. Throughout the wound healing process diabetic animals treated with vehicle exhibited increased wound MAL with reduced VEGF, pAkt, peNOS and nitrite/nitrate, all associated with poor re-epitheliziation, angiogenesis, and wound breaking strength. Cibenitide administration significantly improved these abnormalities. The results suggest that cibinetide-mediated IRR activation may represent an interesting strategy to treat diabetes-associated wound healing. 相似文献
52.
Gabriele Giacomo Schiattarella Fabio Cattaneo Gianluigi Pironti Fabio Magliulo Giuseppe Carotenuto Marinella Pirozzi Roman Polishchuk Domenica Borzacchiello Roberta Paolillo Marco Oliveti Nicola Boccella Marisa Avvedimento Maria Sepe Giuseppe Gargiulo Assunta Lombardi Rosa Anna Busiello Bruno Trimarco Giovanni Esposito Antonio Feliciello Cinzia Perrino 《PloS one》2016,11(7)
53.
Angelica Del Giudice Domenica R. Massardo Filomena Manna Natalia Koltovaya Hans Hartings Luigi Del Giudice Klaus Wolf 《Current microbiology》1997,34(6):382-384
In previous papers (Del Giudice et al. Curr Genet
8:493–497, 1984; Massardo et al. Curr Genet 17:455–457, 1985) we have shown
that strains of Saccharomyces cerevisiae that are devoid of
mitochondrial DNA (rho
o) are resistant to the alkaloid
lycorine isolated from Amaryllis plants, whereas strains containing
mitochondrial DNA (rho
−
, mit
−
,
or rho
+
) are sensitive to this drug. In addition, we were
able to show that the so-called hypersuppressive petites, whose mitochondrial
genomes consist of short regions of DNA containing an ori sequence,
show intermediate resistance. In this paper, we demonstrate that the degree
of suppressiveness of a rho
− mutant correlates with the
degree of resistance to lycorine.
Received: 20 September 1996 / Accepted: 10 January 1997 相似文献
54.
Biancamaria Farina Annarita Del Gatto Daniela Comegna Sonia Di Gaetano Domenica Capasso Carla Isernia Michele Saviano Roberto Fattorusso Laura Zaccaro Luigi Russo 《Journal of peptide science》2019,25(5)
Integrins are heterodimeric cell‐surface proteins that play important roles during developmental and pathological processes. Diverse human pathologies involve integrin adhesion including thrombotic diseases, inflammation, tumour progression, fibrosis, and infectious diseases. Although in the past decade, novel integrin‐inhibitor drugs have been developed for integrin‐based medical applications, the structural determinants modulating integrin‐ligands recognition mechanisms are still poorly understood, reducing the number of integrin subtype exclusive antagonists. In this scenario, we have very recently showed, by means of chemical and biological assays, that a chimeric peptide (named RGDechi), containing a cyclic RGD motif linked to an echistatin C‐terminal fragment, is able to interact with the components of integrin family with variable affinities, the highest for αvβ3. Here, in order to understand the mechanistic details driving the molecular recognition mechanism of αvβ3 by RGDechi, we have performed a detailed structural and dynamics characterization of the free peptide by natural abundance nuclear magnetic resonance (NMR) spectroscopy. Our data indicate that RGDechi presents in solution an heterogeneous conformational ensemble characterized by a more constrained and rigid pentacyclic ring and a largely unstructured acyclic region. Moreover, we propose that the molecular recognition of αvβ3 integrin by RGDechi occurs by a combination of conformational selection and induced fit mechanisms. Finally, our study indicates that a detailed NMR characterization, by means of natural abundance 15N and 13C, of a mostly unstructured bioactive peptide may provide the molecular basis to get essential structural insights into the binding mechanism to the biological partner. 相似文献
55.
Ihssane Bouybayoune Susanna Mantovani Federico Del Gallo Ilaria Bertani Elena Restelli Liliana Comerio Laura Tapella Francesca Baracchi Natalia Fernández-Borges Michela Mangieri Cinzia Bisighini Galina V. Beznoussenko Alessandra Paladini Claudia Balducci Edoardo Micotti Gianluigi Forloni Joaquín Castilla Fabio Fiordaliso Fabrizio Tagliavini Luca Imeri Roberto Chiesa 《PLoS pathogens》2015,11(4)
Fatal familial insomnia (FFI) and a genetic form of Creutzfeldt-Jakob disease (CJD178) are clinically different prion disorders linked to the D178N prion protein (PrP) mutation. The disease phenotype is determined by the 129 M/V polymorphism on the mutant allele, which is thought to influence D178N PrP misfolding, leading to the formation of distinctive prion strains with specific neurotoxic properties. However, the mechanism by which misfolded variants of mutant PrP cause different diseases is not known. We generated transgenic (Tg) mice expressing the mouse PrP homolog of the FFI mutation. These mice synthesize a misfolded form of mutant PrP in their brains and develop a neurological illness with severe sleep disruption, highly reminiscent of FFI and different from that of analogously generated Tg(CJD) mice modeling CJD178. No prion infectivity was detectable in Tg(FFI) and Tg(CJD) brains by bioassay or protein misfolding cyclic amplification, indicating that mutant PrP has disease-encoding properties that do not depend on its ability to propagate its misfolded conformation. Tg(FFI) and Tg(CJD) neurons have different patterns of intracellular PrP accumulation associated with distinct morphological abnormalities of the endoplasmic reticulum and Golgi, suggesting that mutation-specific alterations of secretory transport may contribute to the disease phenotype. 相似文献
56.
This work deals with the Dakin-West synthesis, starting from the nucleoamino acid 1-thyminyl acetic acid, as well the NMR, ESI MS, and X-ray characterization of a heteroaromatic compound denominated by us T(2)CO, comprising two thymine moieties anchored to a 2-propanonic unit, the spectroscopic properties of which were studied by UV as a function of temperature and ionic strength. Preliminary binding-studies with molecules of biomedical interest such as nucleic acids and proteins, performed on samples containing T(2)CO, suggested that this molecule is able to interact very weakly with double-stranded RNA, whereas it does not seem to bind other nucleic acids or proteins. Moreover, by studies with fresh human serum we found that T(2)CO is resistant to enzymatic degradation till 24?h, whereas UV metal binding-studies, performed using solutions of copper (II) chloride dihydrate and nickel (II) chloride hexahydrate, revealed a certain ability of T(2)CO to bind copper (II) cation. Finally, by CD spectroscopy we investigated the influence of T(2)CO on the already described supramolecular networks based on L-serine-containing nucleopeptides. More particularly, we found that T(2)CO is able to increase the level of structuration of the non-covalent supramolecular assembly of the chiral nucleopeptides, which is a feature of remarkable interest for the development of innovative drug delivery tools. 相似文献
57.
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
58.
Discovery and structure–activity relationship of a novel spirocarbamate series of NPY Y5 antagonists
Colin P. Leslie Jonathan Bentley Matteo Biagetti Stefania Contini Romano Di Fabio Daniele Donati Thorsten Genski Sebastien Guery Angelica Mazzali Giancarlo Merlo Domenica A. Pizzi Fabiola Sacco Catia Seri Michela Tessari Laura Zonzini Laura Caberlotto 《Bioorganic & medicinal chemistry letters》2010,20(20):6103-6107
A novel series of trans-8-aminomethyl-1-oxa-3-azaspiro[4.5]decan-2-one derivatives was identified with potent NPY Y5 antagonist activity. Optimization of the original lead furnished compounds 23p and 23u, which combine sub-nanomolar Y5 activity with metabolic stability, oral bioavailability, brain penetration and strong preclinical profile for development. Both compounds significantly inhibited the food intake induced by a Y5 selective agonist with minimal effective doses of 3 mg/kg po. 相似文献
59.
Matteo Biagetti Colin Philip Leslie Angelica Mazzali Catia Seri Domenica Antonia Pizzi Jonathan Bentley Thorsten Genski Romano Di Fabio Laura Zonzini Laura Caberlotto 《Bioorganic & medicinal chemistry letters》2010,20(16):4741-4744
A novel class of small molecule NPY Y5 antagonists based around an azabicyclo[3.1.0]hexane scaffold was identified through modification of a screening hit. Structure–activity relationships and efforts undertaken to achieve a favourable pharmacokinetic profile in rat are described. 相似文献
60.