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31.
COMT polymorphism modulates the resting‐state EEG alpha oscillatory response to acute nicotine in male non‐smokers
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H. Bowers D. Smith S. de la Salle J. Choueiry D. Impey T. Philippe H. Dort A. Millar M. Daigle P. R. Albert A. Beaudoin V. Knott 《Genes, Brain & Behavior》2015,14(6):466-476
Performance improvements in cognitive tasks requiring executive functions are evident with nicotinic acetylcholine receptor (nAChR) agonists, and activation of the underlying neural circuitry supporting these cognitive effects is thought to involve dopamine neurotransmission. As individual difference in response to nicotine may be related to a functional polymorphism in the gene encoding catechol‐O‐methyltransferase (COMT), an enzyme that strongly influences cortical dopamine metabolism, this study examined the modulatory effects of the COMT Val158Met polymorphism on the neural response to acute nicotine as measured with resting‐state electroencephalographic (EEG) oscillations. In a sample of 62 healthy non‐smoking adult males, a single dose (6 mg) of nicotine gum administered in a randomized, double‐blind, placebo‐controlled design was shown to affect α oscillatory activity, increasing power of upper α oscillations in frontocentral regions of Met/Met homozygotes and in parietal/occipital regions of Val/Met heterozygotes. Peak α frequency was also found to be faster with nicotine (vs. placebo) treatment in Val/Met heterozygotes, who exhibited a slower α frequency compared to Val/Val homozygotes. The data tentatively suggest that interindividual differences in brain α oscillations and their response to nicotinic agonist treatment are influenced by genetic mechanisms involving COMT. 相似文献
32.
Agata Rekas Robert B. Knott Anna Sokolova Kevin J. Barnham Keyla A. Perez Colin L. Masters Simon C. Drew Roberto Cappai Cyril C. Curtain Chi L. L. Pham 《European biophysics journal : EBJ》2010,39(10):1407-1419
Inclusions of aggregated α-synuclein (α-syn) in dopaminergic neurons are a characteristic histological marker of Parkinson’s
disease (PD). In vitro, α-syn in the presence of dopamine (DA) at physiological pH forms SDS-resistant non-amyloidogenic oligomers.
We used a combination of biophysical techniques, including sedimentation velocity analysis, small angle X-ray scattering (SAXS)
and circular dichroism spectroscopy to study the characteristics of α-syn oligomers formed in the presence of DA. Our SAXS
data show that the trimers formed by the action of DA on α-syn consist of overlapping worm-like monomers, with no end-to-end
associations. This lack of structure contrasts with the well-established, extensive β-sheet structure of the amyloid fibril
form of the protein and its pre-fibrillar oligomers. We propose on the basis of these and earlier data that oxidation of the
four methionine residues at the C- and N-terminal ends of α-syn molecules prevents their end-to-end association and stabilises
oligomers formed by cross linking with DA-quinone/DA-melanin, which are formed as a result of the redox process, thus inhibiting
formation of the β-sheet structure found in other pre-fibrillar forms of α-syn. 相似文献
33.
Robert G. Doupé Jim Mitchell Matthew J. Knott Aaron M. Davis Alan J. Lymbery 《Wetlands Ecology and Management》2010,18(1):69-78
Foraging by feral pigs can strongly affect wetland vegetation assemblages and so too wider ecological processes, although
their effects on freshwater ecosystems have seldom been studied. We assessed the ecological effects of pig foraging in replicate
fenced and unfenced ephemeral floodplain lagoons in tropical north-eastern Australia. Pig foraging activities in unfenced
lagoons caused major changes to aquatic macrophyte communities and as a consequence, to the proportional amounts of open water
and bare ground. The destruction of macrophyte communities and upheaval of wetland sediments significantly affected wetland
turbidity, and caused prolonged anoxia and pH imbalances in the unfenced treatments. Whilst fencing of floodplain lagoons
will protect against feral pig foraging activities, our repeated measures of many biological, physical and chemical parameters
inferred that natural seasonal (i.e. temporal) effects had a greater influence on these variables than did pigs. To validate
this observation requires measuring how these effects are influenced by the seemingly greater annual disturbance regime of
variable flooding and drying in this tropical climate. 相似文献
34.
35.
Marijn Rutgers Daniël BF Saris Wouter JA Dhert Laura B Creemers 《Arthritis research & therapy》2010,12(3):R114
Introduction
Intraarticular administration of autologous conditioned serum (ACS) recently demonstrated some clinical effectiveness in treatment of osteoarthritis (OA). The current study aims to evaluate the in vitro effects of ACS on cartilage proteoglycan (PG) metabolism, its composition and the effects on synovial fluid (SF) cytokine levels following intraarticular ACS administration. 相似文献36.
Knott ML Matthaei KI Giacomin PR Wang H Foster PS Dent LA 《International journal for parasitology》2007,37(12):1367-1378
Eosinophils are an important feature of immune responses to infections with many of the tissue-invasive helminth parasites. The cytokine IL-5 and a high-affinity double GATA-binding site within the GATA-1 promoter are critical for eosinophilopoiesis. In this study, we believe we demonstrate for the first time that defects in eosinophilopoiesis are associated with impaired resistance to Nippostrongylus brasiliensis. Primary and secondary infections were established in wildtype (WT), IL-5(-/-) and DeltadblGATA mice. Resistance to secondary infections was impaired in IL-5(-/-) and DeltadblGATA mice, with significantly more larvae able to reach the lungs 2 days p.i. Pulmonary inflammation was minimal in all strains in the first 2 days of both primary and secondary infections, suggesting that eosinophil-dependent resistance occurred before larvae reached this site. Intestinal worm burdens and/or parasite egg production in primary infections were greater in animals with defective eosinophilopoiesis. While larvae did reach the gut by day 3 of secondary infections of WT and IL-5(-/-) mice, worms were expelled by day 7, even in the complete absence of eosinophils in tissues of the small intestine. This and our previous studies indicate that N. brasiliensis are likely to be exquisitely sensitive to attack by eosinophils soon after entry into the skin. Eosinophils in the gut may make a modest contribution to resistance on first exposure to the parasite, but are not required for expulsion in either primary or secondary infections. In order to mount an effective immune response it may be vital for the host to identify and attack the parasite before it implements immune evasion strategies and migrates to other anatomical sites. These observations may be of particular significance for the development of successful vaccines against hookworms and other nematodes. 相似文献
37.
Burger K Kieser N Gallinat S Mielke H Knott S Bergemann J 《BioFactors (Oxford, England)》2007,31(3-4):181-190
Animal and human studies have shown that low levels of folic acid are associated with an impaired DNA Repair Capacity (DRC) and an increased cancer risk. However, the molecular evidence that folic acid enhances the DRC of cultured human cells is still limited because of a paucity of in vitro studies. We investigated the effect of folic acid depletion in vitro on the DRC of human dermal fibroblasts derived from 17 donors of different ages. To assess the cellular Nucleotide Excision DRC, we used a modified Host Cell-Reactivation Assay (HCRA), adapted to the Fluorescence Activated Cell Sorting (FACS)-technology, which is highly sensitive in comparison to luminometer-technology and allows single cell based analysis. We used DsRed as a reporter (irradiated with UVC light) and pEGFP to control the performance of the transformations. Folic acid had a statistically significant effect on the DRC in all of the 17 donors, however, the levels varied considerably between individuals (2.0-19.6%). When the effect of folic acid substituted on the DRC was compared to donor age, we observed that there was less DNA repair in old donors compared to the younger donors, although this was only significant at lower levels. 相似文献
38.
39.
R Gon?alves LA Szmuchrowski LS Prado BP Couto JCQ Machado VO Damasceno JA Lamounier 《Biology of sport / Institute of Sport》2015,32(3):255-260
The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children. 相似文献
40.
Huntington''s disease (HD) is an inherited, neurodegenerative disorder caused by a single-gene mutation: a CAG expansion in the huntingtin (HTT) gene that results in production of a mutated protein, mutant HTT, with a polyglutamine tail (polyQ-HTT). Although the molecular pathways of polyQ-HTT toxicity are not fully understood, because protein misfolding and aggregation are central features of HD, it has long been suspected that cellular housekeeping processes such as autophagy might be important to disease pathology. Indeed, multiple lines of research have identified abnormal autophagy in HD, characterized generally by increased autophagic induction and inefficient clearance of substrates. To date, the origin of autophagic dysfunction in HD remains unclear and the search for actors involved continues. To that end, recent studies have suggested a bidirectional relationship between autophagy and primary cilia, signaling organelles of most mammalian cells. Interestingly, primary cilia structure is defective in HD, suggesting a potential link between autophagic dysfunction, primary cilia and HD pathogenesis. In addition, because polyQ-HTT also accumulates in primary cilia, the possibility exists that primary cilia might play additional roles in HD: perhaps by disrupting signaling pathways or acting as a reservoir for secretion and propagation of toxic, misfolded polyQ-HTT fragments. Here, we review recent research suggesting potential links between autophagy, primary cilia and HD and speculate on possible pathogenic mechanisms and future directions for the field. 相似文献