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991.
De Luca A 《Acta myologica》2012,31(1):40-47
Duchenne muscular dystrophy is a lethal X-linked muscle disease affecting 1/3500 live male birth. It results from defects in the subsarcolemmal protein dystrophin, a component of the dystrophin-glycoprotein complex (DGC) which links the intracellular cytoskeleton to the extracellular matrix. The absence of dystrophin leads to muscle membrane fragility, muscle necrosis and gradual replacement of skeletal muscle by fat and connective tissue, through a complex and still unclear cascade of interconnecting events. No cure is currently available, with glucocorticoids being the sole drugs in clinical use in spite of their remarkable side effects. A great effort is devoted at performing pre-clinical tests on the mdx mouse, the mostly used homologous animal model for DMD, with the final aim to identify drugs safer than steroids and able to target the pathogenic mechanisms so to delay pathology progression. This review updates the efforts on this topic, focusing on the open issues about the animal model and highlighting the classes of pharmaceuticals that are more promising as disease-modifiers, while awaiting for more corrective therapies. Although caution is necessary in data transfer from mdx model to DMD patients, the implementation of standard operating procedures and the growing understanding of the pathology may allow a more accurate evaluation of therapeutics, alone or in combination, in pre-clinical settings. A continuous cross-talk with clinicians and patients associations are also crucial points for proper translation of data from mouse to bedside. 相似文献
992.
993.
Annamaria Brioli Lorenzo Melchor Michele Cavo Gareth J. Morgan 《British journal of haematology》2014,165(4):441-454
It is clear that cancers comprise a mixture of clones, a feature termed intra‐clonal heterogeneity, that compete for spatial and nutritional resources in a fashion that leads to disease progression and therapy resistance. This process of competition resembles the schema proposed by Darwin to explain the origin of the species, and applying these evolutionary biology concepts to cancer has the potential to improve our treatment strategies. Multiple myeloma (MM) has a unique set of characteristics that makes it a perfect model in which to study the presence of intra‐clonal heterogeneity and its impact on therapy. Novel therapies have improved the outcome of MM patients, increasing both progression‐free and overall survival. Current therapy comprises an induction, consolidation and maintenance phases and it is important to consider how these components of MM therapy are affected by the presence of intra‐clonal heterogeneity. In this evolutionary context therapy can be considered as a selective pressure differentially acting on the myeloma clones and impacting on their chances of survival. In this review current knowledge of intra‐clonal heterogeneity, as well as its impact on the different components of MM treatment is discussed. 相似文献
994.
Ferdinando Frigeri Gaetana Capobianco Luigi Aloj Francesco Volzone Annarosaria De Chiara Annamaria Bonelli Tindaro Gatani Gianpaolo Marcacci Daniela Donnarumma Cristina Becchimanzi Elisabetta de Lutio Franco Ionna Rosaria De Filippi Secondo Lastoria Antonello Pinto 《British journal of haematology》2014,166(1):118-129
We explored activity and safety of a dose‐dense/dose‐intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVDDD‐DI) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two‐stage Bryant‐Day Phase II study to receive six cycles of ABVDDD‐DI without consolidation radiotherapy. Cycles were supported with granulocyte colony‐stimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m2; first four cycles only). Co‐primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event‐free (EFS) and disease‐free survival (DFS). All patients received the four doxorubicin‐intensified courses and 96% concluded all six cycles (82·3% within the intended 18 weeks). This translated into a 66·9% increase of received dose‐intensity for doxorubicin and 31·8% for the other agents over standard ABVD. The CR rate was 95·1% (78/82) and 87·8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14·6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Five‐year EFS and DFS was 88·3% and 93·7%, respectively. ABVDDD‐DI regimen was well‐tolerated and ensured substantial CR and EFS rates without radiotherapy. 相似文献
995.
996.
Gennaro Galizia Eva Lieto Ferdinando De Vita Francesca Ferraraccio Anna Zamboli Andrea Mabilia Annamaria Auricchio Paolo Castellano Vincenzo Napolitano Michele Orditura 《International journal of colorectal disease》2014,29(1):89-97
Purpose
Complete mesocolic excision (CME) with central vascular ligation (CVL) has been proposed for treatment of colon cancers based on the same principles as total mesorectal excision. Impressive outcomes have been reported, however, direct comparisons with the classic procedure are lacking.Methods
Forty-five consecutive patients operated on in the last 5 years with CME and CVL right hemicolectomy entered the study. Fifty-eight right-sided colon cancer patients operated in the previous 5 years with classic approach constituted the control group. Intra- and postoperative course assessed the safety of the procedure. Primary end-points for oncological adequacy were recurrence and survival rate.Results
All operations were successful with no increase in postoperative complications (p?=?0.85). Number of harvested nodes and length of vascular ligation were shown to be significantly better in the CME group (p?<?0.01). A higher number of tumor deposits were harvested thus allowing chemotherapy in newly upstaged patients. Locoregional recurrences were never experienced in CME patients (p?=?0.03). The risk of cancer-related death was reduced by over one half in all CME patients, and even by three quarters in node-positive tumors. The classic operation was significantly associated with poor outcome (p?<?0.01).Conclusion
This study shows that CME with CVL is a safe and effective surgical approach for right colon cancer, thus confirming the previously reported oncological adequacy. The procedure was shown to significantly decrease local recurrences and to improve the survival rate, particularly in node-positive patients. Urgent diffusion of this technique is warranted. 相似文献997.
Charlotte M. Niemeyer Mignon L. Loh Annamaria Cseh Todd Cooper Christopher C. Dvorak Rebecca Chan Blanca Xicoy Ulrich Germing Seiji Kojima Atsushi Manabe Michael Dworzak Barbara De Moerloose Jan Stary Owen P. Smith Riccardo Masetti Albert Catala Eva Bergstraesser Marek Ussowicz Oskana Fabri André Baruchel Hélène Cavé Michel Zwaan Franco Locatelli Henrik Hasle Marry M. van den Heuvel-Eibrink Christian Flotho Ayami Yoshimi 《Haematologica》2015,100(1):17-22
Juvenile myelomonocytic leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile myelomonocytic leukemia increasingly receive novel agents in phase I–II clinical trials as pre-transplant therapy or therapy for relapse after transplantation. However, response criteria or definitions of outcome for standardized evaluation of treatment effect in patients with juvenile myelomonocytic leukemia are currently lacking. Here we propose criteria to evaluate the response to the non-transplant therapy and definitions of remission status after hematopoietic stem cell transplantation. For the evaluation of non-transplant therapy, we defined 6 clinical variables (white blood cell count, platelet count, hematopoietic precursors and blasts in peripheral blood, bone marrow blast percentage, spleen size and extramedullary disease) and 3 genetic variables (cytogenetic, molecular and chimerism response) which serve to describe the heterogeneous picture of response to therapy in each individual case. It is hoped that these criteria will facilitate the comparison of results between clinical trials in juvenile myelomonocytic leukemia. 相似文献
998.
Leonardo Calo’ Annamaria Martino Claudia Tota Alessandro Fagagnini Renzo Iulianella Marco Rebecchi Luigi Sciarra Giuseppe Giunta Maria Grazia Romano Roberto Colaceci Antonio Ciccaglioni Fabrizio Ammirati Ermenegildo de Ruvo 《World journal of cardiology》2015,7(12):922-930
AIM: To compare the utility of the partners-heart failure (HF) algorithm with the care alert strategy for remote monitoring, in guiding clinical actions oriented to treat impending HF.METHODS: Consecutive cardiac resynchronization-defibrillator recipients were followed with biweekly automatic transmissions. After every transmission, patients received a phone contact in order to check their health status, eventually followed by clinical actions, classified as “no-action”, “non-active” and “active”. Active clinical actions were oriented to treat impending HF. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of the partners-HF algorithm vs care alert in determining active clinical actions oriented to treat pre-HF status and to prevent an acute decompensation, were also calculated.RESULTS: The study population included 70 patients with moderate to advanced systolic HF and QRS duration longer than 120 ms. During a mean follow-up of 8 ± 2 mo, 665 transmissions were collected. No deaths or HF hospitalizations occurred. The sensitivity and specificity of the partners-HF algorithm for active clinical actions oriented to treat impending HF were 96.9% (95%CI: 0.96-0.98) and 92.5% (95%CI: 0.90-0.94) respectively. The positive and negative predictive values were 84.6% (95%CI: 0.82-0.87) and 98.6% (95%CI: 0.98-0.99) respectively. The partners-HF algorithm had an accuracy of 93.8% (95%CI: 0.92-0.96) in determining active clinical actions. With regard to active clinical actions, care alert had a sensitivity and specificity of 11.05% (95%CI: 0.09-0.13) and 93.6% respectively (95%CI: 0.92-0.95). The positive predictive value was 42.3% (95%CI: 0.38-0.46); the negative predictive value was 71.1% (95%CI: 0.68-0.74). Care alert had an accuracy of 68.9% (95%CI: 0.65-0.72) in determining active clinical actions.CONCLUSION: The partners-HF algorithm proved higher accuracy and sensitivity than care alert in determining active clinical actions oriented to treat impending HF. Future studies in larger populations should evaluate partners-HF ability to improve HF-related clinical outcomes. 相似文献
999.
1000.
TRAP1 controls cell cycle G2–M transition through the regulation of CDK1 and MAD2 expression/ubiquitination 下载免费PDF全文
Lorenza Sisinni Francesca Maddalena Valentina Condelli Giuseppe Pannone Vittorio Simeon Valeria Li Bergolis Elvira Lopes Annamaria Piscazzi Danilo Swann Matassa Carmela Mazzoccoli Filomena Nozza Giacomo Lettini Maria Rosaria Amoroso Pantaleo Bufo Franca Esposito Matteo Landriscina 《The Journal of pathology》2017,243(1):123-134