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11.
Gajendiran M 《Brain research bulletin》2008,75(5):674-680
The purpose of the present study was to investigate the 5-HT(2C) receptor-mediated effects on the spinal monosynaptic mass reflex activities and also its functional interactions with 5-HT(1A) receptors in anesthetized, acutely spinalized mammalian adult spinal cord in vivo. Intravenous administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) (0.1 mg/kg), an agonist of 5-HT(2A/2C) receptors, significantly increased the excitability of spinal motoneurons as reflected by an increase in the spinal monosynaptic mass reflex amplitude to 150-200% of the control. 5-HT(2A/2C) receptor-induced motoneuron excitability was slow, persistent and long-lasting for more than 2h that was significantly inhibited by 5-HT(2C) receptor specific antagonist SB 242084 administered 10 min prior to DOI. Simultaneous administration of DOI (0.1 mg/kg, i.v.) along with (+/-)-8-hydroxy dipropylaminotetraline hydrobromide (8-OH-DPAT) (0.1 mg/kg, i.v.) completely inhibited DOI-induced spinal monosynaptic mass reflex facilitation. In another separate study, administration of 8-OH-DPAT (0.1 mg/kg, i.v.) at the maximum response of DOI also inhibited the motoneuron's excitability; however, the inhibition lasted only for a period of 40-60 min after administration of 8-OH-DPAT, after which the spinal monosynaptic mass reflex amplitude reached its maximum level. These findings suggest that the 5-HT(2C) receptor is primarily involved in the mediation of the long-lasting excitability of spinal motoneurons and possibly interacts with its functional counterpart, 5-HT(1A) receptors in the mammalian adult spinal cord. 相似文献
12.
Recent studies have established that the expression of defensive rage behavior in the cat is mediated over a descending pathway from the medial hypothalamus to the dorsolateral quadrant of the midbrain periaqueductal gray matter (PAG). The present study was designed to determine the roles played by 5-HT1A and 5-HT2/1C receptors in this region of PAG in modulating defensive rage behavior elicited from the cat's medial hypothalamus. Monopolar stimulating electrodes were implanted into the medial hypothalamus from which defensive rage behavior could be elicited by electrical stimulation. During the course of the study, the `hissing' component of the defensive rage response was used as a measure of defensive rage behavior. Cannula-electrodes were implanted into sites within the PAG from which defensive rage could also be elicited by electrical stimulation in order that 5-HT compounds could be microinjected into behaviorally identifiable regions of the PAG at a later time. Microinjections of the selective 5-HT1A agonist, (+)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OHDPAT) (50 pmol, 2.0 and 3.0 nmol), into the PAG suppressed the hissing response in a dose-dependent manner. Administration of the selective 5-HT1A antagonist, 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinyl-benzamide hydrochloride (p-MPPI) (1.5 and 3.0 nmol), blocked the suppressive effects of 8-OHDPAT upon hissing. In contrast, microinjections of the 5-HT2/1C receptor agonist (+)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride ((+)-DOI hydrochloride) (0.01, 1.0 and 1.5 nmol) facilitated the occurrence of hissing elicited from the medial hypothalamus in a dose-dependent manner. Immunohistochemical analysis revealed the presence of 5-HT axons and preterminals throughout the PAG, and in particular, in its dorsolateral aspect which receives major inputs from the medial hypothalamus in association with defensive rage behavior. The overall findings of the study provide evidence that activation of 5-HT1A and 5-HT2/1C receptors within the midbrain PAG differentially modulate the expression of defensive rage behavior elicited from the medial hypothalamus of the cat. 相似文献
13.
Low-fluence photodynamic therapy combinations in the treatment of exudative age-related macular degeneration
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AIM: To compare the efficacy of low-fluence photodynamic therapy (PDT) combinations in the treatment of age-related macular degeneration (AMD).
METHODS: Forty-five previously untreated eyes of 45 patients with exudative AMD whose best-corrected visual acuity (BCVA) was ≥0.3 (Snellen) were enrolled. 15 patients in Group I underwent low-fluence PDT (25J/cm2-300mW/cm2-83sec) and intravitreal pegaptanib combination, 15 patients in Group II underwent PDT (50J/cm2-600mW/cm2-83sec) and intravitreal pegaptanib combination while, 15 patients in Group III underwent intravitreal pegaptanib monotherapy. Complete ophthalmologic examinations were performed in pre and post treatment visits, and the results were statistically analised. A clinical activity score (CAS) was calculated by using changes in lesion size, amount of hemorrhage, staining pattern in FA and OCT measurement of intra/subretinal fluid. ≤ 3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment.
RESULTS: The mean age of 19 female (42.2%) and 26 male (57.8%) patients was 72.82±8.02 years. Mean follow-up was 13.93±5.87 months. Lesion type was occult in 28 eyes (62.2%). Treatment success rates according to BCVA assessments were 86.7%, 80%, 60% and mean BCVA decrease were 0.3, 1.0, 2.2 logMAR lines in Group I, II and III, respectively (P>0.05). According to the changes in central macular thickness and CAS, no difference was found among the study groups (P=0.850 and P=0.811, respectively). Patients treated with combination regimens had lower intravitreal injection frequencies (P=0.015).
CONCLUSION: Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD. 相似文献
14.
15.
Mature (3–4 months) and aged (18–19 months) Sprague-Dawley (SD) rats were treated with 5-HT receptor agonists and drug-induced behaviours monitored. The 5-HT2/1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), induced wet dog shakes and back muscle contractions which were significantly increased in aged, compared to mature, rats, suggesting an age-related enhancement of 5-HT2 receptor function. In contrast, the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) induced forepaw treading, flat body posture, hypothermia and hyperactivity which were not significantly different in aged compared to mature rats. Levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and frontal cortex were measured using high performance liquid chromatography with electrochemical detection. There were no age-related changes in hippocampal 5-HT or 5-HIAA. However both 5-HT and 5-HIAA were increased in the frontal cortex of aged SD rats. 8-OH-DPAT reduced 5-HIAA in both regions examined in mature rats, an effect which was attenuated in the aged rats, suggesting an age-related reduction in presynaptic 5-HT1A receptor function. DOI did not induce any changes in 5-HT or 5-HIAA in either of the regions examined. Radioligand binding studies with [3H] ketanserin showed there to be no significant age-related changes in cortical 5-HT2 receptor density or affinity. In the samples taken from mature rats GTP shifted the competition curve to DOI and reduced the proportion of high affinity agonist binding sites; this effect was not observed in the aged samples, suggesting that there may be age-related changes in G-protein-mediated receptor-effector coupling mechanisms. 相似文献
16.
Rationale Selective serotonin reuptake inhibitors and serotonin and noradrenaline reuptake inhibitors demonstrated an anxiolytic-like
effect in the four-plate test (FPT). (+/−)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI; a 5-HT2A receptor agonist) also possessed strong anxiolytic-like effect in the same test. A 5-HT2A mechanism seems to be implicated in the mechanism of action of both antidepressants and DOI in this test. On the other hand,
the α-adrenergic ligands have also demonstrated an activity in other models of anxiety. A previous study demonstrated that
the α2-adrenoceptor agonists abolished the anxiolytic-like effect of antidepressants.
Objectives The aim of the present study was to evaluate the role of noradrenergic system on the regulation of 5-HT2 receptors implicated in the DOI anxiolytic-like activity in the FPT.
Methods First, the effect of noradrenergic and serotonergic lesions on DOI anxiolytic-like activity was studied in the FPT. Second,
the effect of co-administration of α-adrenoceptor ligands and DOI was evaluated in the same test.
Results The noradrenergic and serotonergic lesions had no effect on DOI (1 mg/kg) anti-punishment activity in the FPT. Adrafinil 0.25
and 4 mg/kg (an α1-adrenoceptor agonist), prazosin 0.5 and 2 mg/kg (an α1-adrenoceptor antagonist) and idazoxan 1 and 4 mg/kg (an α2-adrenoceptor antagonist) did not modify the activity of DOI. Clonidine 0.06 mg/kg, guanabenz 0.125 and 0.5 mg/kg (two α2-adrenoceptor agonists) and guanfacine 0.06 and 0.125 mg/kg (a specific α2A-adrenoceptor agonist) completely abolished DOI-induced increase in punished passages.
Conclusion These results indicate that the DOI seems to act on the 5-HT2 receptors post-synaptically located. The effect of DOI is regulated by the α2-adrenoceptors. 相似文献
17.
Seely KA Lapoint J Moran JH Fattore L 《Progress in neuro-psychopharmacology & biological psychiatry》2012,39(2):234-243
"K2" and "Spice" drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as "legal highs". These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate "not for human consumption", the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications. 相似文献
18.
Wada A Kunii Y Ikemoto K Yang Q Hino M Matsumoto J Niwa S 《Progress in neuro-psychopharmacology & biological psychiatry》2012,37(1):8-14
Calcineurin (CaN) has been investigated extensively in numerous biochemical, behavioral, and genetic studies in schizophrenia because its function is closely related to dopamine-glutamate signal transduction, which is thought to be associated with pathophysiological changes in schizophrenia. Although evidence has suggested that dysfunction of CaN may be a risk factor for schizophrenia, there have been few reports focusing on the expression of CaN mRNA and CaN protein levels in the brains of schizophrenic patients. In addition, findings on CaN expression in postmortem brains from patients with schizophrenia have been inconsistent. Here, we conducted immunohistochemical examinations of several regions in postmortem brains, including the dorsolateral prefrontal cortex (DLPFC), hippocampus, caudate nucleus, and putamen, using specific antibodies, and compared the results from the brains of nine schizophrenic subjects to nine age- and sex-matched control subjects. There was no significant difference in the ratio of CaN immunoreactive (IR) neurons between schizophrenia and control groups in the DLPFC or hippocampus, and a significantly increased ratio of CaN-IR neurons was seen in the caudate nucleus in the brains from schizophrenia patients. As the striatum contains most of the brain dopamine, the results of the present study have critical implications and suggest that alterations in CaN signaling in the caudate contribute to the pathogenesis of schizophrenia. This is the first report of caudate CaN abnormalities in schizophrenia. 相似文献
19.
Cervantes-Durán C Vidal-Cantú GC Barragán-Iglesias P Pineda-Farias JB Bravo-Hernández M Murbartián J Granados-Soto V 《Pharmacology, biochemistry, and behavior》2012,102(1):30-35
In this study we assessed the role of local peripheral and spinal serotonin 2B (5-HT2B) receptors in rats submitted to the formalin test. For this, local peripheral ipsilateral, but not contralateral, administration of the highly selective 5-HT2B receptor antagonist 2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyridine (RS-127445, 0.01-1 nmol/paw) significantly prevented 1% formalin-induced flinching behavior. Moreover, local peripheral ipsilateral, but not contralateral, of the selective 5-HT2 receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, 1-10 nmol/paw) augmented 0.5% formalin-induced nociceptive behavior. The local pronociceptive effect of the 5-HT2 receptor agonist DOI (10 nmol/paw) was significantly prevented by the local injection of RS-127445 (0.01 nmol/paw). Moreover, intrathecal injection of the selective 5-HT2B receptor antagonist RS-127445 (0.1-10 nmol/rat) also prevented 1% formalin-induced nociceptive behavior. In contrast, spinal injection of the 5-HT2 receptor agonist DOI (1-10 nmol/rat) significantly increased flinching behavior induced by 0.5% formalin. The spinal pronociceptive effect of the 5-HT2 receptor agonist DOI (10 nmol/rat) was prevented by the intrathecal injection of the 5-HT2B receptor antagonist RS-127445 (0.1 nmol/rat). Our results suggest that the 5-HT2B receptors play a pronociceptive role in peripheral as well as spinal sites in the rat formalin test. 5-HT2B receptors could be a target to develop analgesic drugs. 相似文献
20.
Schindler EA Dave KD Smolock EM Aloyo VJ Harvey JA 《Pharmacology, biochemistry, and behavior》2012,101(1):69-76