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101.
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This paper reports an analysis of a typical case of negative bilateral externality – a situation in which two legitimate activities, fishing and wildlife conservation, each give rise to damages to the other party. The Cornish fishing industry believes that its annual profits are reduced by an estimated £100 000 because of the damage by seal populations to caught fish. About 80 individuals belonging to the Cornish Grey Seal population (of about 400 specimens) are killed as a by-catch of trawling. Thus, the status quo is clearly inefficient: seals are perceived to damage fish and fishermen definitely damage seals. The biological dynamics of the seal population is not absolutely clear, so that a precautionary approach requires that care should be taken to avoid the risk of damaging the population in an irreversible way. Moreover, public opinion considers seals to be a high value flagship species. One of the goals of any conflict resolution should be to capture the economic value of seal conservation – i.e. to convert conservation benefits into resource flows – and use at least part of it in order to create incentives for a more efficient allocation of resources. The authorities should invest in seal conservation (i.e. compensating fishermen) if the benefits deriving from conservation exceed the opportunity costs of conservation. Such a solution clearly requires that the conservation benefits be estimated. To investigate the economic value of seal conservation a contingent valuation study is carried out. A contingent valuation study utilises a questionnaire approach and part of the questionnaire seeks to elicit individuals' willingness to pay (WTP) for a change in the state of some good or asset, in this case seal conservation. Due to resource limitations, the sample size of those interviewed in the study reported is small, so that we cannot be extremely confident about the results. However, they are consistent with those derived from similar studies on flagship species. Results show a mean WTP for recreational use of seals of about £8 per person for the option of seeing seals in a specialised sanctuary for seals recovered from accidents, and closer to £9 for seeing seals in the wild. The annual non-use value of seals – i.e. value unassociated with actual viewing – was found to be £526 000 in the most conservative estimation, aggregated over the Seal Sanctuary visitors. This economic potential could be realised in several ways and used to compensate fishermen for changing fishing techniques, targets and fishing areas. Finally, we investigate the role the Seal Sanctuary is playing in this context and some policy suggestions are discussed. 相似文献
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Valentina Gambino Giulia De Michele Oriella Venezia Pierluigi Migliaccio Valentina Dall'Olio Loris Bernard Simone Paolo Minardi Maria Agnese Della Fazia Daniela Bartoli Giuseppe Servillo Myriam Alcalay Lucilla Luzi Marco Giorgio Heidi Scrable Pier Giuseppe Pelicci Enrica Migliaccio 《Aging cell》2013,12(3):435-445
105.
F Schinzari M Tesauro V Rovella N Di Daniele P Gentileschi N Mores U Campia C Cardillo 《American journal of physiology. Endocrinology and metabolism》2012,303(6):E806-E811
In patients with the metabolic syndrome (MetS), the facilitatory effect of insulin on forearm vasodilator responsiveness to different stimuli is impaired. Whether the RhoA/Rho kinase (ROCK) pathway is involved in this abnormality is unknown. We tested the hypotheses that, in MetS patients, ROCK inhibition with fasudil restores insulin-stimulated vasodilator reactivity and that oxidative stress plays a role in this mechanism. Endothelium-dependent and -independent forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were assessed in MetS patients (n = 8) and healthy controls (n = 5) before and after the addition of fasudil (200 μg/min) to an intra-arterial infusion of insulin (0.1 mU/kg/min). In MetS patients (n = 5), fasudil was also infused without hyperinsulinemia. The possible involvement of oxidative stress in the effect of fasudil during hyperinsulinemia was investigated in MetS patients (n = 5) by infusing vitamin C (25 mg/min). In MetS patients, compared with saline, fasudil enhanced endothelium-dependent and -independent vasodilator responses during insulin infusion (P < 0.001 and P = 0.008, respectively), but not in the absence of hyperinsulinemia (P = 0.25 and P = 0.13, respectively). By contrast, fasudil did not affect vasoreactivity to ACh and SNP during hyperinsulinemia in controls (P = 0.11 and P = 0.56, respectively). In MetS patients, fasudil added to insulin and vitamin C did not further enhance vasodilation to ACh and SNP (P = 0.15 and P = 0.43, respectively). In the forearm circulation of patients with the MetS, ROCK inhibition by fasudil improves endothelium-dependent and -independent vasodilator responsiveness during hyperinsulinemia; increased oxidative stress seems to be involved in the pathophysiology of this phenomenon. 相似文献
106.
Sara Bruschini Simona di Martino Maria Elena Pisanu Luigi Fattore Claudia De Vitis Valentina Laquintana Simonetta Buglioni Eugenio Tabbì Andrea Cerri Paolo Visca Gabriele Alessandrini Francesco Facciolo Christian Napoli Marcella Trombetta Antonio Santoro Anna Crescenzi Gennaro Ciliberto Rita Mancini 《Journal of cellular physiology》2020,235(3):1877-1887
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108.
Sebastin A. Esperante Nathalia Varejo Francisca Pinheiro Ricardo Sant'Anna Juan Romn Luque-Ortega Carlos Alfonso Valentina Sora Elena Papaleo Germn Rivas David Reverter Salvador Ventura 《The Journal of biological chemistry》2021,297(3)
Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by the extracellular deposition of the transport protein transthyretin (TTR) as amyloid fibrils. Despite the progress achieved in recent years, understanding why different TTR residue substitutions lead to different clinical manifestations remains elusive. Here, we studied the molecular basis of disease-causing missense mutations affecting residues R34 and K35. R34G and K35T variants cause vitreous amyloidosis, whereas R34T and K35N mutations result in amyloid polyneuropathy and restrictive cardiomyopathy. All variants are more sensitive to pH-induced dissociation and amyloid formation than the wild-type (WT)-TTR counterpart, specifically in the variants deposited in the eyes amyloid formation occurs close to physiological pHs. Chemical denaturation experiments indicate that all the mutants are less stable than WT-TTR, with the vitreous amyloidosis variants, R34G and K35T, being highly destabilized. Sequence-induced stabilization of the dimer–dimer interface with T119M rendered tetramers containing R34G or K35T mutations resistant to pH-induced aggregation. Because R34 and K35 are among the residues more distant to the TTR interface, their impact in this region is therefore theorized to occur at long range. The crystal structures of double mutants, R34G/T119M and K35T/T119M, together with molecular dynamics simulations indicate that their strong destabilizing effect is initiated locally at the BC loop, increasing its flexibility in a mutation-dependent manner. Overall, the present findings help us to understand the sequence-dynamic-structural mechanistic details of TTR amyloid aggregation triggered by R34 and K35 variants and to link the degree of mutation-induced conformational flexibility to protein aggregation propensity. 相似文献
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Amanda Oldani Mireille Cormont Veronique Hofman Valentina Chiozzi Olivier Oregioni Alexandra Canonici Anna Sciullo Patrizia Sommi Alessia Fabbri Vittorio Ricci Patrice Boquet 《PLoS pathogens》2009,5(10)
Infection with Helicobacter pylori is responsible for gastritis and gastroduodenal ulcers but is also a high risk factor for the development of gastric adenocarcinoma and lymphoma. The most pathogenic H. pylori strains (i.e., the so-called type I strains) associate the CagA virulence protein with an active VacA cytotoxin but the rationale for this association is unknown. CagA, directly injected by the bacterium into colonized epithelium via a type IV secretion system, leads to cellular morphological, anti-apoptotic and proinflammatory effects responsible in the long-term (years or decades) for ulcer and cancer. VacA, via pinocytosis and intracellular trafficking, induces epithelial cell apoptosis and vacuolation. Using human gastric epithelial cells in culture transfected with cDNA encoding for either the wild-type 38 kDa C-terminal signaling domain of CagA or its non-tyrosine-phosphorylatable mutant form, we found that, depending on tyrosine-phosphorylation by host kinases, CagA inhibited VacA-induced apoptosis by two complementary mechanisms. Tyrosine-phosphorylated CagA prevented pinocytosed VacA to reach its target intracellular compartments. Unphosphorylated CagA triggered an anti-apoptotic activity blocking VacA-induced apoptosis at the mitochondrial level without affecting the intracellular trafficking of the toxin. Assaying the level of apoptosis of gastric epithelial cells infected with wild-type CagA+/VacA+
H. pylori or isogenic mutants lacking of either CagA or VacA, we confirmed the results obtained in cells transfected with the CagA C-ter constructions showing that CagA antagonizes VacA-induced apoptosis. VacA toxin plays a role during H. pylori stomach colonization. However, once bacteria have colonized the gastric niche, the apoptotic action of VacA might be detrimental for the survival of H. pylori adherent to the mucosa. CagA association with VacA is thus a novel, highly ingenious microbial strategy to locally protect its ecological niche against a bacterial virulence factor, with however detrimental consequences for the human host. 相似文献