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61.
Walton R Kimber M Rockett K Trafford C Kwiatkowski D Sirugo G 《Nature genetics》2005,37(9):915-6; author reply 916
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Hohmann AG Suplita RL Bolton NM Neely MH Fegley D Mangieri R Krey JF Walker JM Holmes PV Crystal JD Duranti A Tontini A Mor M Tarzia G Piomelli D 《Nature》2005,435(7045):1108-1112
Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target. 相似文献
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Federica Corallini Paola Secchiero Antonio Paolo Beltrami Daniela Cesselli Elisa Puppato Roberto Ferrari Carlo Alberto Beltrami Giorgio Zauli 《Cellular and molecular life sciences : CMLS》2010,67(8):1307-1314
The number of circulating mesenchymal stem cells (MSC), analyzed after acute myocardial infarction (AMI), was lower in AMI
patients who developed heart failure (HF) in the follow-up. Conversely, the circulating levels of tumor necrosis factor (TNF)-α,
and osteoprotegerin (OPG) were higher in AMI patients who developed HF with respect to the patients who did not develop HF.
In vitro exposure to TNF-α enhanced the migration of MSC in response to TNF-related apoptosis-inducing ligand (TRAIL) and
significantly increased the release of OPG by endothelial cells. On the contrary, OPG dose-dependently neutralized the in
vitro pro-migratory activity of TRAIL. Thus, TNF-α exhibits opposite effects on MSC migration driven by TRAIL: it is capable
of potentiating MSC migration as well as of inhibiting MSC migration as an indirect consequence of OPG induction, which might
result in a suboptimal recruitment of circulating MSC after AMI in those patients who develop HF in the follow-up. 相似文献
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Barrett JH Iles MM Harland M Taylor JC Aitken JF Andresen PA Akslen LA Armstrong BK Avril MF Azizi E Bakker B Bergman W Bianchi-Scarrà G Bressac-de Paillerets B Calista D Cannon-Albright LA Corda E Cust AE Dębniak T Duffy D Dunning AM Easton DF Friedman E Galan P Ghiorzo P Giles GG Hansson J Hocevar M Höiom V Hopper JL Ingvar C Janssen B Jenkins MA Jönsson G Kefford RF Landi G Landi MT Lang J Lubiński J Mackie R Malvehy J Martin NG Molven A Montgomery GW van Nieuwpoort FA Novakovic S Olsson H 《Nature genetics》2011,43(11):1108-1113
We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 × 10(-9)), an SNP in MX2 (rs45430, P = 2.9 × 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series. 相似文献
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