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101.
Elisabetta Gabano Sofia Gama Filipa Mendes Marzia B. Gariboldi Elena Monti Sophie Bombard Sabrina Bianco Mauro Ravera 《Journal of biological inorganic chemistry》2013,18(7):791-801
The chemical and biological features of two newly synthesized [PtCl2(L)(2-aminonaphthalene)] complexes (L is NH3 or 2-aminonaphthalene) were compared with those of two already reported enantiomeric complexes of formula [PtCl2(DABN)] [DABN is (R)-1,1′-binaphthyl-2,2′-diamine or (S)-1,1′-binaphthyl-2,2′-diamine]. Solution behavior, lipophilicity, cytotoxicity with regard to one colorectal (HCT116) and two ovarian (A2780 and A2780Cp8) human carcinoma cell lines, and in vitro DNA- and G-quadruplex-binding properties were evaluated. In particular, the cytotoxicity of [PtCl2(NH3)(2-aminonaphthalene)] was better than that of cisplatin for all cell lines, and rather resembled that of oxaliplatin. The solution behavior of the whole series of complexes and the absence of an evident relationship between lipophilicity and cytotoxicity seem to suggest that all these experimental parameters are probably smoothed out during the 3-day cytotoxicity experiments and do not strongly affect the half-maximal inhibitory concentrations. The results of electrophoretic studies indicate that different kinds of interaction with DNA can be involved in the mode of action of these complexes, with intercalation in double-stranded DNA and stacking on G-quadruplex DNA being strongly implicated in particular for [PtCl2(NH3)(2-aminonaphthalene)]. 相似文献
102.
Begoña Prado Villanueva Cornelia Bischoffberger ValdésEmiliana Valderrama Gama Carlos Verdejo BravoJavier Damián 《Revista espa?ola de geriatría y gerontología》2011,46(1):7
Introduction
Urinary incontinence (UI) has been poorly studied in Spanish nursing homes. The objective is to determine the prevalence and related factors of UI in institutionalized older people in Madrid, Spain.Methods
A probabilistic sample of 754 subjects 65 years of age and older living in public and private institutions in Madrid was randomly selected through stratified cluster sampling. Residents, caregivers and physicians were interviewed. UI was defined as any leakage in the previous 14 days. We asked about the frequency (occasional, nocturnal, frequent and total), quantity (drops or small quantities, very much), and types (urge, stress, due to cognitive impairment, and due to walking difficulty). To determine the factors associated with UI, we built logistic regression models that adjusted for age, sex, functional dependency (Barthel index) and cognitive status (Pfeiffer's test).Results
The prevalence of UI was 53.6%. Of all residents 35.8% had frequent or total UI. Among those incontinent 60.1% had a very large quantity of urine loss and the most common presentation was mixed (54.1%). The most frequent type in the population was urgent UI (26.8%) followed by UI due to walking difficulty (21.4%). UI was associated (odds ratios [95% CI]) with moderate (3.51 [1.56-7.89]) and severe functional disability (44.71 [10.99-181.94]), faecal incontinence (4.97 [2.04-12.16]), stroke (4.59 [1.06-19.87]), physical restraints (4.03 [1.02-17.87]), and falls (2.10 [1.16-3.81]). The mean (95% CI) number of pads used per person per day was 3.0 (2.4-3.6).Conclusions
The prevalence of UI was somewhat higher than that of other comparable populations. Mixed forms, including functional types, were common. 相似文献103.
104.
AimsThe effects of several potassium (K+) channel blockers were studied to determine which K+ channels are involved in peripheral antinociception induced by the cannabinoid receptor agonist, anandamide.Main methodsHyperalgesia was induced by subcutaneous injection of 250 μg carrageenan into the plantar surface of the hind paw of rats. The extent of hyperalgesia was measured using a paw pressure test 3 h following carrageenan injection. The weight in grams (g) that elicited a nociceptive response, paw flexion, during the paw pressure test was used as the nociceptive response threshold.Key findingsDoses of 50, 75, and 100 ng of anandamide elicited a dose-dependent antinociceptive effect. Following a 100 ng dose of anandamide no antinociception was observed in the paw that was contralateral to the anandamide injection site, which shows that anandamide has a peripheral site of action. Pretreatment with 20, 40 and 80 μg AM251, a CB1 receptor antagonist, caused a dose-dependent decrease in anandamide-induced antinociception, suggesting that the CB1 receptor is directly involved in anandamide effect. Treatment with 40, 80 and 160 μg glibenclamide, an ATP-sensitive K+ channel blocker, caused a dose-dependent reversal of anandamide-induced peripheral antinociception. Treatment with other K+ channel antagonists, tetraethylammonium (30 μg), paxilline (10 μg) and dequalinium (50 μg), had no effect on the induction of peripheral antinociception by anandamide.SignificanceThis study provides evidence that the peripheral antinociceptive effect of the cannabinoid receptor agonist, anandamide, is primarily caused by activation of ATP-sensitive K+ channels and does not involve other potassium channels. 相似文献
105.
Transforming growth factor beta (TGFbeta) isoforms are known for their antiproliferative effect on epithelial cells in vitro, but the role of each isoform in vivo is poorly understood, mainly when non-pathological conditions are considered. We correlated the presence and distribution of isoforms and receptors to physiological changes in gastric cell proliferation in developing and adult rats. We used fasting to induce either the hyper (14-day-old pups) or hypoproliferation (60-day-old rats) of the gastric epithelium. In 14-d-old pups fasting reduced only TGFbeta3 labelling in the gland. Conversely, in 60-d-old rats there was an increase of TGFbeta1 and TGFbeta3 immunolabelled cells. Receptors were detected at both ages. Therefore, the changes induced by fasting in the constitutive TGFbeta expression can be correlated to the differential epithelial proliferation in the stomach of developing and adult rats. These results suggest that one of the functional roles of TGFbeta in vivo is to locally regulate cell proliferation. 相似文献
106.
Calcified sclerites are common in many benthic marine invertebrates, and despite their widespread occurrence, little is known about their ecological roles. Previous studies suggested that the sclerite composition of coral colonies may be altered in response to environmental cues such as predation and water motion. Furthermore, larger sclerites are thought to be more effective than small ones in deterring predators, while small sclerites may provide greater stiffness and resistance to deformation. The present study compared the length of the sclerites of the sea pansy Renilla muelleri from three depths in Guanabara Bay in southeastern Brazil. Our results show that sclerites are larger in deep-water specimens than in those from shallow water. Field assays were conducted in which sclerites from sea pansies at three depths were incorporated into artificial foods and offered to a natural assemblage of fish. These assays demonstrate that sclerites from R. muelleri from all three depths significantly reduced consumption by generalist carnivorous fishes. We conclude that R. muelleri uses skeletal elements not only to give the body its form but also as a defense against biotic threats. 相似文献
107.
Karina Affeldt Guterres Caroline Bohnen de Matos Luiza Da Gama Osório Isabel Duarte Schuch Marlete Brum Cleff 《Mycopathologia》2014,177(3-4):217-221
Sporotrichosis, caused by the Sporothrix schenckii fungal complex, is a zoonotic mycosis distributed worldwide. Itraconazole is the treatment of choice for domestic animals although some fungal isolates have shown resistance to this drug. The objective of this study was to report, for the first time, the use of (1–3) β-glucan along with itraconazole in the treatment of a canine with sporotrichosis caused by Sporothrix brasiliensis. The animal had ulcerated and crusted lesions, especially on the nasal planum. Clinical samples were collected for a complete blood count, cytological analysis of the lesion, and fungal culture. Based on the results of the laboratory examination, and after the fungal culture, antibiotic therapy and treatment with itraconazole were initiated. Two additional fungal cultures were performed, which were positive. After 7 months of the animal treatment with itraconazole, the S. brasiliensis culture was still positive, so that the itraconazole was associated with (1–3) β-glucan. After four weekly applications of glucan, the complete elimination of the fungus was observed based on the fungal culture negative results. The results show, therefore, that (1–3) β-glucan with itraconazole promoted the case resolution, and it may be considered a promising alternative for the treatment of sporotrichosis in cases of resistance to conventional therapy. 相似文献
108.
Nádia das Dores Moreira Juliana Vitoriano-Souza Bruno Mendes Roatt Paula Melo de Abreu Vieira Henrique Gama Ker Jamille Mirelle de Oliveira Cardoso Rodolfo Cordeiro Giunchetti Cláudia Martins Carneiro Marta de Lana Alexandre Barbosa Reis 《PloS one》2012,7(10)
To develop and test new therapeutics and immune prophylaxis strategies for visceral leishmaniasis (VL), understanding tissue parasitism evolution after experimental infection with Leishmania infantum is important. Experimental infection in a hamster model (Mesocricetus auratus) reproduces several typical aspects of canine and human VL that are closely related to the inoculum’s route. We quantified the parasitism in the liver and spleen of hamsters experimentally infected by various routes (intradermal, intraperitoneal, and intracardiac [IC]) and different strains of L. infantum (MHOM/BR/74/PP75 and Wild) and compared two different methodologies to evaluate tissue parasitism (Leishman Donovan units [LDU] and real-time qPCR). In addition, the quantification of specific total-IgG in the serum of uninfected and infected hamsters was determined by ELISA. The animals were followed for 1, 3, 6 and 9 months post-infection for survival analysis. We found that infection with the Wild strain by the IC route resulted in higher mortality. Positive antibody (IgG) responses were detected with higher peaks at 6 and 9 months in the IC group inoculated with PP75 strain. However, in animals infected with the Wild strain the IgG levels were elevated in all infected groups during all the time evaluated. We also observed by LDU analysis that the IC route lead to higher parasitism in the liver and spleen with both strains. Furthermore, qPCR showed higher sensitivity for identifying animals with low parasitic burden. In conclusion, qPCR can be useful for assessing parasitism in the spleen and liver of a hamster model infected with L. infantum independent of the route of infection, and this technique may become an essential tool for assessing parasite density in the hamster model after experimental treatment or immunization with potential vaccine candidates. 相似文献
109.
Background
Buruli ulcer (BU) is a neglected necrotizing disease of the skin, subcutaneous tissue and bone, caused by Mycobacterium ulcerans. BU pathogenesis is associated with mycolactone, a lipidic exotoxin with cytotoxic and immunosuppressive properties. Since 2004, the World Health Organization recommends the treatment of BU with a combination of rifampicin and streptomycin (RS). Histological analysis of human tissue samples suggests that such antibiotic treatment reverses the mycolactone-induced local immunosuppression, leading to increased inflammatory infiltrations and phagocytosis of bacilli.Methodology/Principal Findings
We used a mouse model of M. ulcerans footpad infection, followed by combined RS treatment. Time-lapsed analyses of macroscopic lesions, bacterial burdens, histology and immunohistochemistry were performed in footpads. We also performed CFU counts, histology and immunohistochemistry in the popliteal draining lymph nodes (DLN). We observed a shift in the cellular infiltrates from a predominantly neutrophilic/macrophagic to a lymphocytic/macrophagic profile in the infected footpads of antibiotic-treated mice. This shift occurred before the elimination of viable M. ulcerans organisms, which were ultimately eradicated as demonstrated by the administration of dexamethasone. This reduction of bacillary loads was accompanied by an increased expression of inducible nitric oxide synthase (NOS2 or iNOS). Predominantly mononuclear infiltrates persisted in the footpads during and after treatment, coincident with the long persistence of non-viable poorly stained acid-fast bacilli (AFB). We additionally observed that antibiotherapy prevented DLN destruction and lymphocyte depletion, which occurs during untreated experimental infections.Conclusions/Significance
Early RS treatment of M. ulcerans mouse footpad infections results in the rapid elimination of viable bacilli with pathogen eradication. However, non-viable AFB persisted for several months after lesion sterilization. This RS regimen prevented DLN destruction, allowing the rapid re-establishment of local and regional cell mediated immune responses associated with macrophage activation. Therefore it is likely that this re-establishment of protective cellular immunity synergizes with antibiotherapy. 相似文献110.
Amparo M. Martínez Luis T. Gama Javier Ca?ón Catarina Ginja Juan V. Delgado Susana Dunner Vincenzo Landi Inmaculada Martín-Burriel M. Cecilia T. Penedo Clementina Rodellar Jose Luis Vega-Pla Atzel Acosta Luz A. álvarez Esperanza Camacho Oscar Cortés Jose R. Marques Roberto Martínez Ruben D. Martínez Lilia Melucci Guillermo Martínez-Velázquez Jaime E. Mu?oz Alicia Postiglioni Jorge Quiroz Philip Sponenberg Odalys Uffo Axel Villalobos Delsito Zambrano Pilar Zaragoza 《PloS one》2012,7(11)