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21.
Few conventional cytotoxic anticancer therapeutics induce immunogenic cell death (ICD). This means that they induce tumor cells to undergo apoptosis while eliciting the emission of a spatiotemporal-defined combination of damage-associated molecular patterns (DAMPs) decoded by the immune system to activate antitumor immunity effective for long-term therapeutic success. The neurotoxin capsaicin (CPS) can induce both cancer cell apoptosis and immune-mediated tumor regression. In the present study, we investigated whether CPS is capable of eliciting the emission of ICD hallmarks in human bladder cancer cell lines undergoing apoptosis. We demonstrated that CPS induces pre- and early apoptotic cell surface exposure of calreticulin (CRT), HSP90, and HSP70 as well as ATP release. Moreover, CRT exposure was prevented by inhibition of endoplasmic reticulum–Golgi traffic by brefeldin A. Furthermore, high-mobility group box 1, HSP90, and HSP70 were passively released at late apoptotic stages. We provide the first evidence that CPS is an inducer of ICD hallmarks, suggesting CPS as a novel potential immunogenic cytotoxic agent. 相似文献
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Gloria Taliani Martina Spaziante Elisa Biliotti Marina Borro Donatella Palazzo Stefania Grieco Cristiana Franchi Giancarlo Iaiani Caterina Furlan Valentina Gallinaro Maurizio Simmaco 《PloS one》2013,8(8)
Background
Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients.Aims
The aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects.Methods and patients
We enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects.Results
CC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p = 0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p = 0.02). Hepatic steatosis did not correlate with IL28B genotype (p = 0,14) but only with a high body mass index (BMI) value (p = 0.03).Conclusions
Female subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile. 相似文献24.
25.
Guang Yang Concetta De Santi Donatella de Pascale Sandra Pucciarelli Stefania Pucciarelli Cristina Miceli 《Biochimie》2013
The ciliated protozoon Euplotes focardii, originally isolated from the coastal seawaters of Terra Nova Bay in Antarctica, shows a strictly psychrophilic phenotype, including optimal survival and multiplication rates at 4–5 °C. This characteristic makes E. focardii an ideal model species for identifying the molecular bases of cold adaptation in psychrophilic organisms, as well as a suitable source of novel cold-active enzymes for industrial applications. In the current study, we characterized the patatin-like phospholipase from E. focardii (EfPLP), and its enzymatic activity was compared to that of the homologous protein from the mesophilic congeneric species Euplotes crassus (EcPLP). Both EfPLP and EcPLP have consensus motifs conserved in other patatin-like phospholipases. 相似文献
26.
Kristina Zakharova Donatella Tesei Gorji Marzban Jan Dijksterhuis Timon Wyatt Katja Sterflinger 《Mycopathologia》2013,175(5-6):537-547
Black microcolonial fungi (MCF) and black yeasts are among the most stress-resistant eukaryotic organisms known on Earth. They mainly inhabit bare rock surfaces in hot and cold deserts of all regions of the Earth, but some of them have a close phylogenetic relation to human pathogenic black fungi which makes them important model organisms also with respect to clinical mycology. The environment of those fungi is especially characterized by extreme changes from humidity to long periods of desiccation and extreme temperature differences. A key to the understanding of MCF ecology is the question about metabolic activity versus dormancy in the natural environments. In this study, the time lag from the desiccated state to rehydration and full metabolic activity and growth was measured and defined in accordance with simulated environmental conditions. The ability to survive after desiccation and the speed of rehydration as well as changes of the whole cell protein pattern are demonstrated. Whereas both mesophilic strains—Exophiala jeanselmei and Knufia perforans (=Coniosporium perforans)—show a clear reaction toward desiccation by production of small proteins, Cryomyces antarcticus—the extremotolerant MCF—does not show any response to desiccation but seems just to down-regulate its metabolism. Data on intracellular sugar suggest that both trehalose and mannitol might play a cell protective role in those fungi. 相似文献
27.
Donatella Camerino Paul Maurice Conway Samantha Sartori Paolo Campanini Madeleine Estryn‐Béhar Beatrice Isabella Johanna Maria van der Heijden 《Chronobiology international》2013,30(2-3):425-442
Satisfactory work ability is sustained and promoted by good physical and mental health and by favorable working conditions. This study examined whether favorable and rewarding work‐related factors increased the work ability among European nurses. The study sample was drawn from the Nurses' Early Exit Study and consisted of 7,516 nursing staff from seven European countries working in state‐owned and private hospitals. In all, 10.8% were day, 4.2% were permanent night, 20.9% were shift without night shift, and 64.1% were shift workers with night shifts. Participants were administered a composite questionnaire at baseline (Time 0) and 1 yr later (Time 1). The Work Ability Index (WAI) at Time 1 was used as the outcome measure, while work schedule, sleep, rewards (esteem and career), satisfaction with pay, work involvement and motivation, and satisfaction with working hours at Time 0 were included as potential determinants of work ability. Univariate and multivariate analyses were conducted after adjusting for a number of confounders (i.e., country, age, sex, type of employment, family status, and other job opportunities in the same area). Work schedule was not related to Time 1 changes in WAI. Higher sleep quality and quantity and more favorable psychosocial factors significantly increased work ability levels. Higher sleep quality and quantity did not mediate the effect of work schedule on work ability. No relevant interaction effects on work ability were observed between work schedule and the other factors considered at Time 0. As a whole, sleep and satisfaction with working time were gradually reduced from day work to permanent night work. However, scores on work involvement, motivation, and satisfaction with pay and rewards were the highest in permanent night workers and the lowest in rotating shift workers that included night shifts. 相似文献
28.
Odile Francesca Restaino Irene di Lauro Donatella Cimini Elisabetta Carlino Mario De Rosa Chiara Schiraldi 《Applied microbiology and biotechnology》2013,97(4):1699-1709
Chondroitin sulfate is a well-known bioactive molecule, widely used as an anti-osteoarthritis drug, that is nowadays mainly produced by animal tissue sources with unsafe extraction procedures. Recent studies have explored an integrated biotechnological–chemical strategy to obtain a chondroitin sulfate precursor from Escherichia coli K4 capsular polysaccharide, demonstrating the influence of environmental and growth conditions on capsule synthesis. In this research work, the flexibility of the strain biosynthetic machinery was investigated to enhance the K4 capsular polysaccharide production by supplementing the growth medium with the monosaccharides (glucuronic acid, galactosamine and fructose) that constitute the chain. Shake flask experiments were performed by adding the sugars singularly or together, by testing monosaccharide different concentrations and times of addition and by observing the bacterial sugar consumption. A K4 capsular polysaccharide production enhancement, compared to the control, was observed in all cases of supplementation and, in particular, significant 68 and 57 % increases were observed when adding 0.385 mM glucuronic acid plus galactosamine or 0.385 mM fructose, respectively. Increased expression levels of the gene kfoC, coding for a K4 polymerase, evaluated in different growth conditions, confirmed the results at the molecular level. Furthermore, batch fermentations, performed in lab-scale reactors (2 L), allowed to double the K4 capsular polysaccharide production values obtained in shake flask conditions, by means of a strict control of the growth parameters. 相似文献
29.
Tiziana Bozzini Giorgia Botta Michela Delfino Silvano Onofri Raffaele Saladino Donatella Amatore Rossella Sgarbanti Lucia Nencioni Anna Teresa Palamara 《Bioorganic & medicinal chemistry》2013,21(24):7699-7708
Catechol derivatives with lipophilic properties have been selectively synthesized by tyrosinase in high yield avoiding long and tedious protection/deprotection steps usually required in traditional procedures. The synthesis was effective also with immobilized tyrosinase able to perform for more runs. The novel catechols were evaluated against influenza A virus, that continue to represent a severe threat worldwide. A significant antiviral activity was observed in derivatives characterized by antioxidant activity and long carbon alkyl side-chains, suggesting the possibility of a new inhibition mechanism based on both redox and lipophilic properties. 相似文献
30.
Concetta De Santi Hanna-Kirsti S. Leiros Alessia Di Scala Donatella de Pascale Bjørn Altermark Nils-Peder Willassen 《Extremophiles : life under extreme conditions》2016,20(3):323-336
A gene encoding an esterase, ThaEst2349, was identified in the marine psychrophilic bacterium Thalassospira sp. GB04J01. The gene was cloned and overexpressed in E. coli as a His-tagged fusion protein. The recombinant enzyme showed optimal activity at 45 °C and the thermal stability displayed a retention of 75 % relative activity at 40 °C after 2 h. The optimal pH was 8.5 but the enzyme kept more than 75 % of its maximal activity between pH 8.0 and 9.5. ThaEst2349 also showed remarkable tolerance towards high concentrations of salt and it was active against short-chain p-nitrophenyl esters, displaying optimal activity with the acetate. The enzyme was tested for tolerance of organic solvents and the results are suggesting that it could function as an interesting candidate for biotechnological applications. The crystal structure of ThaEst2349 was determined to 1.69 Å revealing an asymmetric unit containing two chains, which also is the biological unit. The structure has a characteristic cap domain and a catalytic triad comprising Ser158, His285 and Asp255. To explain the cold-active nature of the enzyme, we compared it against thermophilic counterparts. Our hypothesis is that a high methionine content, less hydrogen bonds and less ion pairs render the enzyme more flexible at low temperatures. 相似文献