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921.
Francesca Trojsi Giuseppina Caiazzo Daniele Corbo Giovanni Piccirillo Viviana Cristillo Cinzia Femiano Teresa Ferrantino Mario Cirillo Maria Rosaria Monsurrò Fabrizio Esposito Gioacchino Tedeschi 《PloS one》2015,10(3)
Neurodegenerative process in amyotrophic lateral sclerosis (ALS) has been proven to involve several cortical and subcortical brain regions within and beyond motor areas. However, how ALS pathology spreads progressively during disease evolution is still unknown. In this cross-sectional study we investigated 54 ALS patients, divided into 3 subsets according to the clinical stage, and 18 age and sex-matched healthy controls, by using tract-based spatial statistics (TBSS) diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analyses. We aimed to identify white (WM) and gray matter (GM) patterns of disease distinctive of each clinical stage, corresponding to specific clinical milestones. ALS cases in stage 2A (i.e., at diagnosis) were characterized by GM and WM impairment of left motor and premotor cortices and brainstem at ponto-mesenchephalic junction. ALS patients in clinical stage 2B (with impairment of two functional regions) exhibited decreased fractional anisotropy (FA) (p<0.001, uncorrected) and increased mean (MD) and radial diffusivity (RD) (p<0.001, uncorrected) in the left cerebellar hemisphere and brainstem precerebellar nuclei, as well as in motor areas, while GM atrophy (p<0.001, uncorrected) was detected only in the left inferior frontal gyrus and right cuneus. Finally, ALS patients in stage 3 (with impairment of three functional regions) exhibited decreased FA and increased MD and RD (p<0.05, corrected) within WM underneath bilateral pre and postcentral gyri, corpus callosum midbody, long associative tracts and midbrain, while no significant clusters of GM atrophy were observed. Our findings reinforce the hypothesis that the neurodegenerative process propagates along the axonal pathways and develops beyond motor areas from early stages, involving progressively several frontotemporal regions and their afferents and efferents, while the detection of GM atrophy in earlier stages and its disappearance in later stages may be the result of reactive gliosis. 相似文献
922.
Alessia Verduri Fabrizio Luppi Roberto D’Amico Sara Balduzzi Roberto Vicini Anna Liverani Valentina Ruggieri Mario Plebani Maria Pia Foschino Barbaro Antonio Spanevello Giorgio Walter Canonica Alberto Papi Leonardo Michele Fabbri Bianca Beghè 《PloS one》2015,10(3)
Background
The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD.Methods and Findings
We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], −7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days.Conclusions
Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098).Trial Registration
ClinicalTrials.gov NCT01125098 相似文献923.
Ross SH Lindsay Y Safrany ST Lorenzo O Villa F Toth R Clague MJ Downes CP Leslie NR 《Cellular signalling》2007,19(7):1521-1530
The Protein Tyrosine Phosphatase (PTP) family comprises a large and diverse group of enzymes, regulating a range of biological processes through de-phosphorylation of many proteins and lipids. These enzymes share a catalytic mechanism that requires a reduced and reactive cysteine nucleophile, making them potentially sensitive to inactivation and regulation by oxidation. Analysis of ten PTPs identified substantial differences in the sensitivity of these enzymes to oxidation in vitro. More detailed experiments confirmed the following rank order of sensitivity: PTEN and Sac1>PTPL1/FAP-1>myotubularins. When the apparent sensitivity to oxidation of these PTPs in cells treated with hydrogen peroxide was analysed, this correlated well with the observed sensitivities to oxidation in vitro. These data suggested that different PTPs may fall into at least three different classes with respect to mechanisms of cellular redox regulation. 1. PTEN and Sac1 were readily and reversibly oxidised in vitro and in cells treated with hydrogen peroxide 2. PTPL1 appeared to be resistant to oxidation in cells, correlating with its sensitivity to reduction by glutathione in vitro 3. The myotubularin family of lipid phosphatases was almost completely resistant to oxidation in vitro and in cells. Our results show that sensitivity to reversible oxidation is not a necessary characteristic of the PTPs and imply that such sensitivity has evolved as a regulatory mechanism for some of this large family, but not others. 相似文献
924.
This study aims to establish the contribution of the water soluble and water insoluble organic fractions to total oxygen uptake
rate during high rate composting process of a mixture of organic fraction of municipal solid waste and lignocellulosic material.
This mixture was composted using a 20 l self-heating pilot scale composter for 250 h. The composter was fully equipped to
record both the biomass-temperature and oxygen uptake rate. Representative compost samples were taken at 0, 70, 100, 110,
160, and 250 h from starting time. Compost samples were fractionated in water soluble and water insoluble fractions. The water
soluble fraction was then fractionated in hydrophilic, hydrophobic, and neutral hydrophobic fractions. Each fraction was then
studied using quantitative (total organic carbon) and qualitative analysis (diffuse reflectance infrared spectroscopy and
biodegradability test). Oxygen uptake rates were high during the initial stages of the process due to rapid degradation of
the soluble degradable organic fraction (hydrophilic plus hydrophobic fractions). Once this fraction was depleted, polymer
hydrolysis accounted for most of the oxygen uptake rate. Finally, oxygen uptake rate could be modeled using a two term kinetic.
The first term provides the oxygen uptake rate resulting from the microbial growth kinetic type on easily available, no-limiting
substrate (soluble fraction), while the second term considers the oxygen uptake rate caused by the degradation of substrate
produced by polymer hydrolysis. 相似文献
925.
Hamprecht D Micheli F Tedesco G Checchia A Donati D Petrone M Terreni S Wood M 《Bioorganic & medicinal chemistry letters》2007,17(2):428-433
Two independent approaches resulted in the identification of a series of isoindolone derivatives as potent and selective 5-HT2C antagonists. From a Medicinal Chemistry perspective this template was considered interesting as it allowed the incorporation of the carbon-carbon double bond of an earlier dihydropyrrolone series in an aromatic system within a comparatively simple and compact motif. Additionally an in silico screening approach of the corporate database using a 5-HT2C pharmacophore model resulted in the identification of a related structure containing this template. The strategy used to optimise potency at the target receptor and to improve the pharmacokinetic profile is described, resulting in molecules combining high potency with good selectivity and oral bioavailability. 相似文献
926.
Micheli F Cavanni P Di Fabio R Donati D Hamdan M Provera S Tranquillini ME Vitulli G 《Bioorganic & medicinal chemistry letters》2007,17(4):969-973
Following the recent disclosure of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester as a potent and selective mGluR1 non-competitive antagonist, the use of a doubly (13)C-labeled analogue to identify, and consequently prevent, metabolically labile positions is reported. 相似文献
927.
In summer 2003 two separate infestations due to the common bedbug (Cimex lectularius) occurred in Pisa, Italy. Cutaneous reaction was evident and one patient developed a severe bullous eruption. In both cases there was circumstantial evidence for association with international travel. 相似文献
928.
929.
930.
Prevention of amyloid-like aggregation as a driving force of protein evolution 总被引:3,自引:0,他引:3
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Uncontrolled protein aggregation is a constant challenge in all compartments of living organisms. The failure of a peptide or protein to remain soluble often results in pathology. So far, more than 40 human diseases have been associated with the formation of extracellular fibrillar aggregates - known as amyloid fibrils - or structurally related intracellular deposits. It is well known that molecular chaperones and elaborate quality control mechanisms exist in the cell to counteract aggregation. However, an increasing number of reports during the past few years indicate that proteins have also evolved structural and sequence-based strategies to prevent aggregation. This review describes these strategies and the selection pressures that exist on protein sequences to combat their uncontrolled aggregation. We will describe the different types of mechanism evolved by proteins that adopt different conformational states including normally folded proteins, intrinsically disordered polypeptide chains, elastomeric systems and multimodular proteins. 相似文献