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排序方式: 共有75条查询结果,搜索用时 15 毫秒
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David R Owen Qi Guo Nicola J Kalk Alessandro Colasanti Dimitra Kalogiannopoulou Rahul Dimber Yvonne L Lewis Vincenzo Libri Julien Barletta Joaquim Ramada-Magalhaes Aruloly Kamalakaran David J Nutt Jan Passchier Paul M Matthews Roger N Gunn Eugenii A Rabiner 《Journal of cerebral blood flow and metabolism》2014,34(6):989-994
Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [11C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (VND), and hence estimate the BPND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [11C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, VND was estimated via the occupancy plot. Values of BPND for all subjects were calculated using this VND estimate. Total volume of distribution (VT) of MABs (2.94±0.31) was lower than VT of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a VND estimate of 1.98 (1.69, 2.26). Based on these VND estimates, BPND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [11C]PBR28 VND and hence BPND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating VND for TSPO targeting radioligands. 相似文献
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Nicholas Jones Marcus J Messenger Michael J O'Neill Anna Oldershaw Gary Gilmour Rosa M A Simmons Smriti Iyengar Vincenzo Libri Mark Tricklebank Steve C R Williams 《Neuropsychopharmacology》2008,33(7):1713-1723
We present a substantial series of behavioral and imaging experiments, which demonstrate, for the first time, that increasing AMPA receptor-mediated neurotransmission via administration of potent and selective biarylsulfonamide AMPA potentiators LY404187 and LY451395 reverses the central effects of an acutely intoxicating dose of ethanol in the rat. Using pharmacological magnetic resonance imaging (phMRI), we observed that LY404187 attenuated ethanol-induced reductions in blood oxygenation level dependent (BOLD) in the anesthetized rat brain. A similar attenuation was apparent when measuring local cerebral glucose utilization (LCGU) via C14-2-deoxyglucose autoradiography in freely moving conscious rats. Both LY404187 and LY451395 significantly and dose-dependently reversed ethanol-induced deficits in both motor coordination and disruptions in an operant task where animals were trained to press a lever for food reward. Both prophylactic and acute intervention treatment with LY404187 reversed ethanol-induced deficits in motor coordination. Given that LY451395 and related AMPA receptor potentiators/ampakines are tolerated in both healthy volunteers and elderly patients, these data suggest that such compounds may form a potential management strategy for acute alcohol intoxication. 相似文献
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Bruno T De Angelis R De Nicola F Barbato C Di Padova M Corbi N Libri V Benassi B Mattei E Chersi A Soddu S Floridi A Passananti C Fanciulli M 《Cancer cell》2002,2(5):387-399
DNA tumor virus oncoproteins bind and inactivate Rb by interfering with the Rb/HDAC1 interaction. Che-1 is a recently identified human Rb binding protein that inhibits the Rb growth suppressing function. Here we show that Che-1 contacts the Rb pocket region and competes with HDAC1 for Rb binding site, removing HDAC1 from the Rb/E2F complex in vitro and from the E2F target promoters in vivo. Che-1 overexpression activates DNA synthesis in quiescent NIH-3T3 cells through HDAC1 displacement. Consistently, Che-1-specific RNA interference affects E2F activity and cell proliferation in human fibroblasts but not in the pocket protein-defective 293 cells. These findings indicate the existence of a pathway of Rb regulation supporting Che-1 as the cellular counterpart of DNA tumor virus oncoproteins. 相似文献
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M Lima A Morabito M Libri M Bertozzi M Dòmini V Lauro C Strano P Messina G Tani 《Zeitschrift für Kinderchirurgie》2000,10(4):265-269
The authors refer to the use of the laparoscopic approach in Persistent Mullerian Duct Syndrome, starting from a case of "male vagina" with an anomaly inserted left ductus deferens inside the mullerian persistent duct. This patient was operated on using the laparoscopic technique. 相似文献
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Rationale Drugs that enhance α-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid (AMPA) receptor-mediated glutamatergic transmission,
such as the AMPA receptor potentiator LY404187, may form treatment strategies for disorders of cognition, learning and memory.
Objectives Pharmacological magnetic resonance imaging (phMRI) uses blood oxygenation level dependent (BOLD) contrast as a marker of neuronal
activity and allows dynamic non-invasive in vivo imaging of the effects of CNS-active compounds. This study used phMRI to
examine the effects of LY404187 in the rat brain.
Method Groups of Sprague Dawley rats (n=7) were anaesthetised and placed in a 4.7 Tesla superconducting magnet before receiving an
acute dose of LY404187 (0.5 mg/kg s.c.), either alone or after pretreatment with the selective AMPA/kainate antagonist LY293558
(15 mg/kg s.c.), or LY293558 alone (15 mg/kg s.c.). Brain images were acquired for each subject every minute for 180 min.
These volumes were extensively pre-processed before being analysed for changes in BOLD contrast.
Results LY404187 produced significant increases in BOLD contrast in brain regions including the hippocampus, lateral and medial habenulae
and superior and inferior colliculi. These changes were blocked by LY293558. When administered alone, LY293558 caused widespread
decreases in BOLD contrast.
Conclusions The known actions of LY404187 suggest the observed BOLD signal increases reflect increases in excitatory neurotransmission.
The decreases in signal following LY293558 alone are harder to interpret and are discussed in terms of the negative BOLD response.
This study provides the first evidence that the effects of AMPA receptor-mediating compounds can be observed using phMRI. 相似文献
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G. B. De Sarro G. Bagetta C. Ascioti V. Libri G. Nistic 《British journal of pharmacology》1989,96(1):59-64
1. Pertussis toxin, a substance which interferes selectively with receptor-mediated signal transduction mechanisms, was injected into the locus coeruleus of rats 1, 2, 3, 6 or 10 days before the microinjection of clonidine or yohimbine into the same site. 2. Clonidine produced in control rats typical behavioural sedation and/or sleep and ECoG synchronization while yohimbine produced behavioural arousal and ECoG desynchronization. 3. The behavioural and ECoG effects of both compounds were blocked in animals pretreated with pertussis toxin. This activity was more marked from 2 to 6 days after pertussis toxin pretreatment and was restored 10 days after toxin administration. In addition, the behavioural and ECoG slow-wave sleep observed after intraperitoneal administration of clonidine (0.2 mumol kg-1) was significantly reduced by prior (3 days) microinfusion of pertussis toxin into the locus coeruleus. 4. These results are consistent with the hypothesis that the behavioural and ECoG effects of clonidine and yohimbine are mediated via a guanine regulatory protein which is affected by pertussis toxin. 相似文献