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1.
Catecholamine receptor binding in rat kidney: effect of aging 总被引:2,自引:0,他引:2
Binding to several receptors was compared in kidneys from 3- and 24-month-old rats. In crude membrane preparations of aged rat kidneys, the number of beta 2-adrenergic receptors was significantly reduced but the number of total beta-adrenoceptors was unchanged. The high-affinity alpha 1-adrenoceptor component was significantly reduced in old rats, whereas the low-affinity component was unchanged. The number of alpha 2-adrenoceptors showed a non-significant decrease. 3H-spiperone binding sites were similar in young and old rats. For each receptor binding the KD values were the same in young and old animals. The D1 dopamine receptor was significantly reduced in old rats. In our experiments, age-related changes of specific binding sites in the kidney were selective for some receptors studied and did not seem to be due to general aging-induced membrane modifications. Moreover, the renal and central receptors were sensitive to aging differently in the same animal model. 相似文献
2.
Caterina Montani Carola Canella Adam J. Schwarz Jennifer Li Gary Gilmour Alberto Galbusera Keith Wafford Daniel Gutierrez-Barragan Andrew McCarthy David Shaw Karen Knitowski David McKinzie Alessandro Gozzi Christian Felder 《Neuropsychopharmacology》2021,46(6):1194
Cholinergic drugs acting at M1/M4 muscarinic receptors hold promise for the treatment of symptoms associated with brain disorders characterized by cognitive impairment, mood disturbances, or psychosis, such as Alzheimer’s disease or schizophrenia. However, the brain-wide functional substrates engaged by muscarinic agonists remain poorly understood. Here we used a combination of pharmacological fMRI (phMRI), resting-state fMRI (rsfMRI), and resting-state quantitative EEG (qEEG) to investigate the effects of a behaviorally active dose of the M1/M4-preferring muscarinic agonist xanomeline on brain functional activity in the rodent brain. We investigated both the effects of xanomeline per se and its modulatory effects on signals elicited by the NMDA-receptor antagonists phencyclidine (PCP) and ketamine. We found that xanomeline induces robust and widespread BOLD signal phMRI amplitude increases and decreased high-frequency qEEG spectral activity. rsfMRI mapping in the mouse revealed that xanomeline robustly decreased neocortical and striatal connectivity but induces focal increases in functional connectivity within the nucleus accumbens and basal forebrain. Notably, xanomeline pre-administration robustly attenuated both the cortico-limbic phMRI response and the fronto-hippocampal hyper-connectivity induced by PCP, enhanced PCP-modulated functional connectivity locally within the nucleus accumbens and basal forebrain, and reversed the gamma and high-frequency qEEG power increases induced by ketamine. Collectively, these results show that xanomeline robustly induces both cholinergic-like neocortical activation and desynchronization of functional networks in the mammalian brain. These effects could serve as a translatable biomarker for future clinical investigations of muscarinic agents, and bear mechanistic relevance for the putative therapeutic effect of these class of compounds in brain disorders.Subject terms: Schizophrenia, Translational research, Preclinical research 相似文献
3.
Morigi M Galbusera M Binda E Imberti B Gastoldi S Remuzzi A Zoja C Remuzzi G 《Blood》2001,98(6):1828-1835
Verotoxin-1 (VT-1)-producing Escherichia coli is the causative agent of postdiarrheal hemolytic uremic syndrome (D+HUS) of children, which leads to renal and other organ microvascular thrombosis. Why thrombi form only on arterioles and capillaries is not known. This study investigated whether VT-1 directly affected endothelial antithrombogenic properties promoting platelet deposition and thrombus formation on human microvascular endothelial cell line (HMEC-1) under high shear stress. Human umbilical vein endothelial cells (HUVECs) were used for comparison as a large-vessel endothelium. HMEC-1 and HUVECs were pre-exposed for 24 hours to increasing concentrations of VT-1 (2-50 pM) and then perfused at 60 dynes/cm(2) with heparinized human blood prelabeled with mepacrine. Results showed that VT-1 significantly increased platelet adhesion and thrombus formation on HMEC-1 in comparison with unstimulated control cells. An increase in thrombus formation was also observed on HUVECs exposed to VT-1, but to a remarkably lower extent. The greater sensitivity of HMEC-1 to the toxin in comparison with HUVECs was at least in part due to a higher expression of VT-1 receptor (20-fold more) as documented by FACS analysis. The HMEC-1 line had a comparable susceptibility to the thrombogenic effect of VT-1 as primary human microvascular cells of the same dermal origin (HDMECs). The adhesive molecules involved in VT-induced thrombus formation were also studied. Blocking the binding of von Willebrand factor to platelet glycoprotein Ib by aurintricarboxylic acid (ATA) or inhibition of platelet alpha(IIb)beta(3)-integrin by chimeric 7E3 Fab resulted in a significant reduction of VT-1-induced thrombus formation, suggesting the involvement of von Willebrand factor-platelet interaction at high shear stress in this phenomenon. Functional blockade of endothelial beta(3)-integrin subunit, vitronectin receptor, P-selectin, and PECAM-1 with specific antibodies was associated with a significant decrease of the endothelial area covered by thrombi. Confocal microscopy studies revealed that VT-1 increased the expression of vitronectin receptor and P-selectin and redistributed PECAM-1 away from the cell-cell border of HMEC-1, as well as of HDMECs, thus indicating that the above endothelial adhesion molecules are directly involved and possibly determine the effect of VT-1 on enhancing platelet adhesion and thrombus formation in microvascular endothelium. These results might help to explain why thrombi in HUS localize in microvessels rather than in larger ones and provide insights on the molecular events involved in the process of microvascular thrombosis associated with D+HUS. 相似文献
4.
Zagra Antonino Scaramuzzo Laura Galbusera Fabio Minoia Leone Archetti Marino Giudici Fabrizio 《European spine journal》2015,24(7):924-930
Introduction
Aim of the study was to evaluate the biomechanical stability and the clinical efficacy of a lumbar interbody fusion obtained by single oblique cage implanted by a posterior approach.Method
Through the realization of three finite element models (FEMs), the biomechanics of POLIF was compared to PLIF and TLIF. Ninety-four patients underwent interbody fusion by POLIF with instrumented posterolateral fusion. Clinical and radiographic outcomes were evaluated at regular intervals for at least 6 months.Results
The FEMs showed no statistically significant differences in stability in compression and flexion–extension. Mean preoperative VAS score was 7.1, decreased to 2.1 at follow-up. Mean preoperative SF-12 value was 34.5 %, increased to 75.4 % at follow-up. All patients showed a good fusion rate and no hardware failure.Discussion
POLIF associated to instrumented posterolateral fusion is a viable and safe surgical technique, which ensures a biomechanical stability similar to other surgical techniques.5.
F Errico V D'Argenio F Sforazzini F Iasevoli M Squillace G Guerri F Napolitano T Angrisano A Di Maio S Keller D Vitucci A Galbusera L Chiariotti A Bertolino A de Bartolomeis F Salvatore A Gozzi A Usiello 《Translational psychiatry》2015,5(2):e512
Increasing evidence points to a role for dysfunctional glutamate N-methyl-D-aspartate receptor (NMDAR) neurotransmission in schizophrenia. D-aspartate is an atypical amino acid that activates NMDARs through binding to the glutamate site on GluN2 subunits. D-aspartate is present in high amounts in the embryonic brain of mammals and rapidly decreases after birth, due to the activity of the enzyme D-aspartate oxidase (DDO). The agonistic activity exerted by D-aspartate on NMDARs and its neurodevelopmental occurrence make this D-amino acid a potential mediator for some of the NMDAR-related alterations observed in schizophrenia. Consistently, substantial reductions of D-aspartate and NMDA were recently observed in the postmortem prefrontal cortex of schizophrenic patients. Here we show that DDO mRNA expression is increased in prefrontal samples of schizophrenic patients, thus suggesting a plausible molecular event responsible for the D-aspartate imbalance previously described. To investigate whether altered D-aspartate levels can modulate schizophrenia-relevant circuits and behaviors, we also measured the psychotomimetic effects produced by the NMDAR antagonist, phencyclidine, in Ddo knockout mice (Ddo−/−), an animal model characterized by tonically increased D-aspartate levels since perinatal life. We show that Ddo−/− mice display a significant reduction in motor hyperactivity and prepulse inhibition deficit induced by phencyclidine, compared with controls. Furthermore, we reveal that increased levels of D-aspartate in Ddo−/− animals can significantly inhibit functional circuits activated by phencyclidine, and affect the development of cortico–hippocampal connectivity networks potentially involved in schizophrenia. Collectively, the present results suggest that altered D-aspartate levels can influence neurodevelopmental brain processes relevant to schizophrenia. 相似文献
6.
Galbusera M Bresin E Noris M Gastoldi S Belotti D Capoferri C Daina E Perseghin P Scheiflinger F Fakhouri F Grünfeld JP Pogliani E Remuzzi G 《Blood》2005,106(3):925-928
Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. The presence of anti-ADAMTS13 autoantibodies is considered a factor predisposing to relapses. Despite close monitoring and intensive plasma treatment, in these patients acute episodes are still associated with substantial morbidity and mortality rates, and the optimal therapeutic option should be prevention of relapses. This study was conducted in a patient with recurrent TTP due to high titers of ADAMTS13 inhibitors, who used to have 2 relapses of TTP a year. The study compared the standard treatment plasma exchange with rituximab. Results documented that plasma exchange had only a small transient effect on ADAMTS13 activity and inhibitors; on the contrary, prophylaxis with rituximab was associated with disappearance of anti-ADAMTS13 antibodies, a progressive recovery of protease activity, and it allowed the patient to maintain a disease-free state during a more than 2-year follow-up. 相似文献
7.
8.
Objective: We sought to assess the efficacy of a manualized body-oriented psychotherapy (BPT) intervention for schizophrenia, by focusing on improvement of negative symptoms and on changes in interactional synchrony. We also explored aspects of a phenomenological theory of schizophrenia, which states that negative symptoms should be understood within an encompassing disturbance of subjectivity and intersubjectivity. Method: Sixteen persons with schizophrenia participated in 10 weeks of BPT. General psychiatric symptomatology and negative symptoms were assessed before and after therapy. Interactional synchrony was assessed via cross-correlations of movements between patient and interviewer in interviews conducted before and after therapy. Results: Psychiatric symptomatology and negative symptoms significantly improved with a medium effect size. We also demonstrated a significant increase in interactional synchrony with a strong effect size. Post hoc analyses showed a significant increase only with open-ended interviews conducted by the same interviewer. Furthermore, we explored the correlation between negative symptoms and interactional synchrony, finding a large inverse relationship. Conclusions: BPT for schizophrenia may effectively reduce patients’ negative symptoms and psychiatric symptomatology. Moreover, it may yield some recovery of pre-reflective social relations. Further evidence of the specific relation between negative symptoms and interactional synchrony would support a phenomenologically informed holistic view of schizophrenia. 相似文献
9.
10.