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排序方式: 共有781条查询结果,搜索用时 15 毫秒
81.
Natalia P. Schütz Paola Ochoa Patricio Duarte Guillermina Remaggi Sebastián Yantorno Ariel Corzo Soledad Zabaljauregui Claudia Shanley Sergio Lopresti Sergio Orlando Verónica Verri Luis Quiroga Carlos A. García Vanesa Fernández Dorotea Fantl 《Hematological oncology》2020,38(3):363-371
Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs. 相似文献
82.
In this study, we have used a combination of immunocytochemical and Ca(2+) imaging techniques to determine the functional localisation of insulin receptors as well as the potential role for insulin in modulating hippocampal synaptic activity. Comparison of insulin receptor and MAP2 labelling demonstrated extensive insulin receptor immunoreactivity on the soma and dendrites of cultured hippocampal neurones. Dual labelling with synapsin 1 also showed punctate insulin receptor labelling associated with synapses. In functional studies, insulin inhibited spontaneous Ca(2+) oscillations evoked in cultured hippocampal neurones following Mg(2+) removal. This action of insulin was mimicked by the ATP-sensitive K(+) (K(ATP)) channel opener diazoxide or the large conductance Ca(2+)-activated K(+) (BK) channel activator NS-1619. Furthermore, application of the K(ATP) channel blocker glybenclamide or the BK channel inhibitors iberiotoxin or charybdotoxin attenuated the actions of insulin, whereas prior incubation with a combination of glybenclamide and iberiotoxin completely blocked insulin action. The ability of insulin to modulate the Ca(2+) oscillations was reduced by the inhibitors of MAPK activation PD 98059 and U0126, but not by the PI 3-kinase inhibitors LY 294002 or wortmannin, indicating that a MAPK-driven process underlies insulin action. In conclusion, insulin inhibits spontaneous Ca(2+) oscillations via a process involving MAPK-driven activation of BK and K(ATP) channels. This process may be a useful therapeutic target for the treatment of epilepsy and certain neurodegenerative diseases. 相似文献
83.
Neutrophils have been implicated in the pathogenesis of several inflammatory lung disorders including asthma, emphysema, and adult respiratory distress syndrome. The precursors of these destructive cells are thought to be marginating neutrophils that, although intravascular, remain intimately associated with endothelium, resisting the shearing forces of flowing blood. The purposes of this study were (1) to examine a method for quantitating marginating lung neutrophils, (2) to assess the adherence of marginating neutrophils to normal lung endothelium, and (3) to determine the reversibility of neutrophil-endothelial cell adherence. Rats were anesthetized and ventilated, and their lungs were exposed through a median sternotomy. The left lung was tied off with blood in situ and the right lung was perfused intraarterially with colloid for 2 minutes. In separate experiments, both left and right lungs were perfused intraarterially with colloid for 25 minutes. Myeloperoxidase, a neutrophil granule enzyme, was related to lung neutrophils. Dithionite-sensitive optical density (DSOD) was related to lung hemoglobin. Marginating lung neutrophils were quantitated by measuring the peroxidase activity of normal blood-perfused lung (myeloperoxidase assay) and subtracting from it the fraction of activity corresponding to the lung blood content (DSOD). The marginating neutrophil pool was identified by 2.1 units myeloperoxidase (5 x 10(6) neutrophils) per gm wet lung. Although the marginating pool was depleted by 54% during 2 minutes of lung colloid perfusion, lung erythrocytes (DSOD) were decreased by a significantly greater 93% (p less than 0.05). Lungs perfused with colloid for 25 minutes had negligible remaining myeloperoxidase activity. We conclude that (1) marginating lung neutrophils can be quantitated with the myeloperoxidase and DSOD assays, (2) marginating neutrophils are relatively adherent to normal lung endothelium compared with intravascular erythrocytes, and (3) the adherence of marginating neutrophils is fully reversible. 相似文献
84.
R. A. Flavin F. Fleming L. Shanley I. P. Kelly 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2004,14(2):84-88
Despite the implication that the clavicle acts as an osseus strut to maintain the width of the shoulder and therefore provide power and stability to the arm-trunk mechanism, there have been inconsistent findings on whether shortening or malunion after clavicle fractures has an effect on shoulder function. We used the Biodex isokinetic assessment and the Constant and Murley scoring system to evaluate shoulder function in patients 3 years after unilateral closed midclavicular fractures (Allman type 1) who were treated nonoperatively. We confined our study group to patients between the ages of 18 and 37 years. The mean degree of shortening was 15 mm, and the mean degree of angular malunion was 13.9°; there was a 74% rate of malunion and a 3% rate of nonunion. The isokinetic function of the shoulder was significantly reduced on the injured side independent of hand dominance. Shortening, angular deformity, and malunion were not associated with this reduction in shoulder function. However, patients with a high degree of shortening and angular malunion reported significantly higher levels of symptoms despite no significant difference in isokinetic function. 相似文献
85.
J L Rodriguez C G Miller L E DeForge L Kelty C J Shanley R H Bartlett D G Remick 《The Journal of trauma》1992,33(1):74-81; discussion 81-2
One hundred five (70%) of 151 patients hospitalized in the intensive care unit and undergoing mechanical ventilation had bronchial secretions that tested positive for interleukin-8 within 36 hours of admission. Arterial blood, mixed venous blood, and urine collected simultaneously all tested negative, except for 11 patients admitted with intra-abdominal septic foci. The presence of interleukin-8 in the pulmonary air space early in the course of hospitalization was significantly associated with patients with multiple injuries, the need for greater ventilatory support, the occurrence of pulmonary dysfunction, and a 66% incidence of nosocomial bacterial pneumonia. We conclude that the early local production of interleukin-8 in the lungs is an early marker of pulmonary injury and may be involved in the pathogenesis of nosocomial bacterial pneumonia. 相似文献
86.
Alison Cole BN RGN & Eamon Shanley RN CPN RNT CPsychol AFBPs S BA MSc PhD 《Journal of advanced nursing》1998,27(6):1171-1176
The development of the extended role in nursing has been seen by some as primarily a means for nurses taking on tasks that have traditionally been the work of junior doctors. Others object to this view and ascribe to the 'new nursing' perspective of Salvage. She sees the extended role as moving towards increasing autonomy and operating in a professional rather than a bureaucratic occupational model. This view militates against the development of nurses as mini-doctors. This paper discusses the controversy surrounding the development of the extended role, focusing particularly on the use of complementary therapies as a legitimate component of the 'new nurses' role. 相似文献
87.
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89.
Cytomegalovirus (CMV) is a major source of morbidity for immunocompromised patients, such as AIDS patients. The folic acid antagonists have not been explored as potential antiviral agents against CMV. We examined the effects of methotrexate, compared to acyclovir and ganciclovir, on both murine CMV (MCMV) and human CMV (HCMV) in vitro. Using a plaque assay in mouse embryo cells or human foreskin fibroblasts for MCMV and HCMV respectively, we found that methotrexate, in micromolar concentrations, was a potent inhibitor of both viruses. This effect was due to folic acid antagonism since folinic acid abrogated the antiviral effect of methotrexate, but not ganciclovir. Cellular toxicity due to methotrexate appeared insufficient to account for the antiviral effects. The ability of methotrexate to inhibit CMV in vivo merits exploration. 相似文献
90.