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排序方式: 共有127条查询结果,搜索用时 15 毫秒
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Le Gouill S Kr?ger N Dhedin N Nagler A Bouabdallah K Yakoub-Agha I Kanouni T Bulabois CE Tournilhac O Buzyn A Rio B Moles MP Shimoni A Bacher U Ocheni S Milpied N Harousseau JL Moreau P Leux C Mohty M 《Annals of oncology》2012,23(10):2695-2703
Background Despite therapeutic approach that combines rituximab-containing chemotherapy, followed or not by autologous stem cell transplantation (auto-SCT), mantle cell lymphoma (MCL) patients experience relapses. Reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) at time of relapse may represent an attractive strategy. Patients and methods We report a multicenter retrospective analysis. Seventy MCL patients underwent RIC-allo-SCT in 12 centers. Results Median age at transplantation was 56 years and median time from diagnosis to transplantation was 44 months. The median number of previous therapies was 2 (range, 1-5) including autologous transplantation in 47 cases. At time of transplantation, 35 patients were in complete remission, 20 were in partial response and 15 in stable disease or progressive disease. The median follow-up for living patients was 24 months. The 2-year event-free survival (EFS) and overall survival (OS) rates were 50% and 53%, respectively. The 1- and 2-year transplant-related mortality rates were 22% and 32%, respectively. The statistical analysis demonstrated that disease status at transplantation was the only parameter influencing EFS and OS. Conclusions These results suggest that RIC-allo-SCT may be an effective therapy in MCL patients with a chemo-sensitive disease at time of transplantation, irrespective of the number of lines of prior therapy. Studies are warranted to investigate the best type of RIC regimen. 相似文献
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Jie Bu Karen M Ashe John Bringas John Marshall James C Dodge Mario A Cabrera-Salazar John Forsayeth Edward H Schuchman Krystof S Bankiewicz Seng H Cheng Lamya S. Shihabuddin Marco A Passini 《Molecular therapy》2012,20(10):1893-1901
Niemann-Pick disease Type A (NPA) is a neuronopathic lysosomal storage disease (LSD)
caused by the loss of acid sphingomyelinase (ASM). The goals of the current study are to
ascertain the levels of human ASM that are efficacious in ASM knockout (ASMKO) mice, and
determine whether these levels can be attained in non-human primates (NHPs) using a
multiple parenchymal injection strategy. Intracranial injections of different doses of
AAV1-hASM in ASMKO mice demonstrated that only a small amount of enzyme (<0.5 mg hASM/g
tissue) was sufficient to increase survival, and that increasing the amount of hASM did
not enhance this survival benefit until a new threshold level of >10 mg hASM/g tissue
was reached. In monkeys, injection of 12 tracts of AAV1-hASM resulted in efficacious
levels of enzyme in broad regions of the brain that was aided, in part, by axonal
transport of adeno-associated virus (AAV) and movement through the perivascular space.
This study demonstrates that a combination cortical, subcortical, and cerebellar injection
protocol could provide therapeutic levels of hASM to regions of the NHP brain that are
highly affected in NPA patients. The information from this study might help design new
AAV-mediated enzyme replacement protocols for NPA and other neuronopathic LSDs in future
clinical trials. 相似文献
25.
Marco A. Passini Jie Bu Eric M. Roskelley Amy M. Richards S. Pablo Sardi Catherine R. O’Riordan Katherine W. Klinger Lamya S. Shihabuddin Seng H. Cheng 《The Journal of clinical investigation》2010,120(4):1253-1264
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by a deficiency of survival motor neuron (SMN) due to mutations in the SMN1 gene. In this study, an adeno-associated virus (AAV) vector expressing human SMN (AAV8-hSMN) was injected at birth into the CNS of mice modeling SMA. Western blot analysis showed that these injections resulted in widespread expression of SMN throughout the spinal cord, and this translated into robust improvement in skeletal muscle physiology, including increased myofiber size and improved neuromuscular junction architecture. Treated mice also displayed substantial improvements on behavioral tests of muscle strength, coordination, and locomotion, indicating that the neuromuscular junction was functional. Treatment with AAV8-hSMN increased the median life span of mice with SMA-like disease to 50 days compared with 15 days for untreated controls. Moreover, injecting mice with SMA-like disease with a human SMN–expressing self-complementary AAV vector — a vector that leads to earlier onset of gene expression compared with standard AAV vectors — led to improved efficacy of gene therapy, including a substantial extension in median survival to 157 days. These data indicate that CNS-directed, AAV-mediated SMN augmentation is highly efficacious in addressing both neuronal and muscular pathologies in a severe mouse model of SMA. 相似文献
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Lamya Alomair Sabeena Mustafa Mohsin Saleet Jafri Wardah Alharbi Abdulrhman Aljouie Fahad Almsned Mohammed Alawad Yahya Abdulfattah Bokhari Mamoon Rashid 《Viruses》2022,14(11)
Protein phosphorylation is a post-translational modification that enables various cellular activities and plays essential roles in protein interactions. Phosphorylation is an important process for the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To shed more light on the effects of phosphorylation, we used an ensemble of neural networks to predict potential kinases that might phosphorylate SARS-CoV-2 nonstructural proteins (nsps) and molecular dynamics (MD) simulations to investigate the effects of phosphorylation on nsps structure, which could be a potential inhibitory target to attenuate viral replication. Eight target candidate sites were found as top-ranked phosphorylation sites of SARS-CoV-2. During the process of molecular dynamics (MD) simulation, the root-mean-square deviation (RMSD) analysis was used to measure conformational changes in each nsps. Root-mean-square fluctuation (RMSF) was employed to measure the fluctuation in each residue of 36 systems considered, allowing us to evaluate the most flexible regions. These analysis shows that there are significant structural deviations in the residues namely nsp1 THR 72, nsp2 THR 73, nsp3 SER 64, nsp4 SER 81, nsp4 SER 455, nsp5 SER284, nsp6 THR 238, and nsp16 SER 132. The identified list of residues suggests how phosphorylation affects SARS-CoV-2 nsps function and stability. This research also suggests that kinase inhibitors could be a possible component for evaluating drug binding studies, which are crucial in therapeutic discovery research. 相似文献
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Rossi JF Fegueux N Lu ZY Legouffe E Exbrayat C Bozonnat MC Navarro R Lopez E Quittet P Daures JP Rouillé V Kanouni T Widjenes J Klein B 《Bone marrow transplantation》2005,36(9):771-779
Interleukin-6 (IL-6) is a major survival factor for multiple myeloma (MM) cells preventing apoptosis induced by dexamethasone (DEX) or chemotherapy. In all, 24 consecutive patients with MM in first-line therapy received DEX for 4 days, followed by melphalan (HDM: 140 mg/m2) and autologous stem cell transplantation (ASCT). The anti-IL-6 monoclonal antibody (mAb) (B-E8) was given till haematological recovery, starting 1 day before DEX. Results were historically compared to MM patients treated with HDM 140 and 200 mg/m2. Our results show (1) that B-E8 was able to fully neutralize IL-6 activity in vivo before and after HDM as shown by inhibition of C reactive protein (CRP) production; (2) no haematological toxicity; (3) a significant reduction of mucositis and fever; (4) a median event-free survival of 35 months and an overall survival of 68.2% at 5 years with a median follow-up of 72 months; and (5) the overall daily IL-6 production progressively increased on and after 7 days post-HDM, with the increased serum CRP levels. In the 5/24 patients with uncontrolled CRP production, a large IL-6 production was detected (320 microg/day) that could not possibly be neutralized by B-E8. These data show the feasibility to neutralize IL-6 in vivo with anti-IL-6 mAb in the context of HDM. 相似文献
30.
F. Rouibaa L. Amrani N. Kanouni N. Amrani 《Journal Africain d'Hépato-Gastroentérologie》2008,2(4):167-169
Behçet’s disease (BD) is a vasculitis characterized by oral and genital ulcers and uveitis. Involvement of the digestive tract is called entero-Behçet’s disease. The most frequent sites of gastrointestinal involvement are the colon and the ileocecal region. Gastric involvement is rarely seen. We report the case of a 45-year-old man with a history of Behçet’s disease, in whom an upper gastrointestinal endoscopy performed because of gastric pain revealed a large gastric ulcer which was diagnosed as related to Behçet’s disease. 相似文献