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11.
Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells 总被引:8,自引:0,他引:8 下载免费PDF全文
Klebanoff CA Gattinoni L Torabi-Parizi P Kerstann K Cardones AR Finkelstein SE Palmer DC Antony PA Hwang ST Rosenberg SA Waldmann TA Restifo NP 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(27):9571-9576
Central memory CD8+ T cells (T(CM)) and effector memory CD8+ T cells (T(EM)) are found in humans and mice; however, their relative contributions to host immunity have only recently been examined in vivo. Further, the ability of T(CM) to treat an established tumor or infection has yet to be evaluated. To address the therapeutic potential of different tumor-reactive CD8+ T cell memory subsets, we used an established model for the in vitro generation of T(CM) and T(EM) by using IL-15 and IL-2, respectively. Adoptively transferred T(CM) exhibited a potent in vivo recall response when combined with tumor-antigen vaccination and exogenous IL-2, leading to the eradication of large established tumors. By contrast, T(EM) were far less effective on a per-cell basis. Microarray analysis revealed that the signature of highly in vivo effective antitumor T cells included the overexpression of genes responsible for trafficking to secondary lymphoid tissues. This gene expression profile correctly predicted the in vitro and in vivo lymphoid-homing attributes of tumor-reactive T cells. Furthermore, we found that homing to secondary lymphoid tissue is required for optimal tumor treatment. Our findings indicated that highly in vivo effective antitumor T cells were those that initially targeted secondary lymphoid tissue, rather than tumor sites, as had previously been postulated. Thus, tumor-reactive CD8+ T cell populations with the phenotypic and functional attributes of T(CM) may be superior to T(EM)/effector T cells for adoptive immunotherapies using concomitant tumor-antigen vaccination. 相似文献
12.
Normalizing Glutamine Concentration Causes Mitochondrial Uncoupling in an In Vitro Model of Human Skeletal Muscle 下载免费PDF全文
Adela Krajcova MD Jakub Ziak Katerina Jiroutkova MD Jana Patkova Moustafa Elkalaf MD Valer Dzupa MD PhD Jan Trnka MD PhD Frantisek Duska MD PhD 《JPEN. Journal of parenteral and enteral nutrition》2015,39(2):180-189
Background: Glutamine has been considered essential for rapidly dividing cells, but its effect on mitochondrial function is unknown. Materials and Methods: Human myoblasts were isolated from skeletal muscle biopsy samples (n = 9) and exposed for 20 days to 6 different glutamine concentrations (0, 100, 200, 300, 500, and 5000 µM). Cells were trypsinized and manually counted every 5 days. Seven days before the end of exposure, half of these cells were allowed to differentiate to myotubes. Afterward, energy metabolism in both myotubes and myoblasts was assessed by extracellular flux analysis (Seahorse Biosciences, Billerica, MA). The protocol for myoblasts was optimized in preliminary experiments. To account for different mitochondrial density or cell count, data were normalized to citrate synthase activity. Results: Fastest myoblast proliferation was observed at 300 µM glutamine, with a significant reduction at 0 and 100 µM. Glutamine did not influence basal oxygen consumption, anaerobic glycolysis or respiratory chain capacity. Glutamine significantly (P = .015) influenced the leak through the inner mitochondrial membrane. Efficiency of respiratory chain was highest at 200–300 µM glutamine (~90% of oxygen used for adenosine triphosphate synthesis). Increased glutamine concentration to 500 or 5000 µM caused mitochondrial uncoupling in myoblasts and myotubes, decreasing the efficiency of the respiratory chain to ~70%. Conclusion: Glutamine concentrations, consistent with moderate clinical hypoglutaminemia (300 µM), bring about an optimal condition of myoblast proliferation and for efficiency of aerobic phosphorylation in an in vitro model of human skeletal muscle. These data support the hypothesis of hypoglutaminemia as an adaptive phenomenon in conditions leading to bioenergetic failure (eg, critical illness). 相似文献
13.
Davel LE Rimmaudo L Español A de la Torre E Jasnis MA Ribeiro ML Gotoh T de Lustig ES Sales ME 《Angiogenesis》2004,7(1):45-51
Neoangiogenesis is essential for tumor and metastasis growth, but this complex process does not follow the same activation pathway, at least in tumor cell lines originated from different murine mammary adenocarcinomas. LMM3 cells were the most potent to stimulate new blood vessel formation. This response was significantly reduced by preincubating cells with indomethacin and NS-398, non-selective cyclooxygenase (COX) and COX-2 selective inhibitors, respectively. COX-1 and COX-2 isoenzymes were both highly expressed in LMM3 cells, and we observed that indomethacin was more effective than NS-398 to inhibit prostaglandin E2 (PGE2) synthesis. In addition, nitric oxide synthase (NOS) inhibitors, Nomega monomethyl L-arginine and aminoguanidine, also reduced LMM3-induced angiogenesis and nitric oxide (NO) synthesis as well. NOS2 > NOS3 proteins and arginase II isoform were detected in LMM3 cells by Western blot. The latter enzyme was also involved in the LMM3 neovascular response, since the arginase inhibitor, Nomega hydroxy L-arginine reduced the angiogenic cascade. On the other hand, parental LM3 cells were able to stimulate neovascularization via COX-1 and arginase products since only indomethacin and Nomega hydroxy L-arginine, which diminished PGE2 and urea synthesis, respectively, also reduced angiogenesis. In turn, LM2 cells angiogenic response could be due in fact to PGE2-induced VEGF liberation that stimulated neoangiogenesis at very low levels of NO. 相似文献
14.
Fernández Patón Matías Cerdá Alberich Leonor Sangüesa Nebot Cinta Martínez de las Heras Blanca Veiga Canuto Diana Cañete Nieto Adela Martí-Bonmatí Luis 《Journal of digital imaging》2021,34(5):1134-1145
Journal of Digital Imaging - Several noise sources, such as the Johnson–Nyquist noise, affect MR images disturbing the visualization of structures and affecting the subsequent extraction of... 相似文献
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Laura Villarreal‐Martínez Jaime García‐Chvez Berenice Snchez‐Jara Aida Mashenka Moreno‐Gonzlez Janet Soto‐Padilla Efraín Aquino‐Fernndez Rogelio Paredes‐Aguilera Karla Maldonado‐Silva Cecilia Rodríguez‐Castillejos Ana Itamar Gonzlez‐vila María Mora‐Torres Hector Manuel Tiznado‐García Natalia Elizabeth Padilla‐Durn Nuria Citlali Luna‐Silva Eric Israel Gutirrez‐Jurez Jorge Nemi‐Cueto Claudia Sofia Gmez‐Gonzlez Ricardo De Len‐Figueroa Adela Lpez‐Miranda Mirna Guadalupe Ríos‐Osuna Edna Liliana Tamez‐Gmez Elio Aarn Reyes‐Espinoza Irving Armando Domínguez‐Varela Gerardo Gonzlez‐Martínez Elias Adn Godoy‐Salinas 《Haemophilia》2020,26(2):290-297
17.
Anne‐Maree Kelly Oene Van Meer Gerben Keijzers Justina Motiejunaite Peter Jones Richard Body Simon Craig Mehmet Karamercan Sharon Klim Veli‐Pekka Harjola Franck Verschuren Anna Holdgate Michael Christ Adela Golea Colin A. Graham Jean Capsec Cinzia Barletta Luis Garcia‐Castrillo Win S. Kuan Said Laribi 《Internal medicine journal》2020,50(2):200-208
18.
Azeez Butali Satoshi Suzuki Margaret E. Cooper Adela M. Mansilla Karen Cuenco Elizabeth J. Leslie Yasushi Suzuki Teruyuki Niimi Masahiko Yamamoto Gongorjav Ayanga Tudevdorj Erkhembaatar Hiroo Furukawa Kumiko Fujiwawa Hideto Imura Aline L. Petrin Nagato Natsume Terri H. Beaty Mary L. Marazita Jeffery C. Murray M.D. 《American journal of medical genetics. Part A》2013,161(5):965-972
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M. Adela Valero M. Victoria Periago Ignacio Pérez‐Crespo Esperanza Rodríguez M. Jesús Perteguer Teresa Gárate Eva M. González‐Barberá Santiago Mas‐Coma 《Tropical medicine & international health : TM & IH》2012,17(5):630-636
Objectives To improve the diagnosis of human fascioliasis caused by Fasciola hepatica and Fasciola gigantica, we evaluated the diagnostic accuracy of an enzyme‐linked immunosorbent assay (ELISA), with Fasciola antigen from the adult liver fluke, for the detection of IgG against fascioliasis in human sera. Methods The sera of 54 fascioliasis cases, originating from three endemic areas, were used in this evaluation: (i) a hyperendemic F. hepatica area where humans usually shed a great number of parasite eggs in faeces (11 sera); (ii) an epidemic F. hepatica area where humans usually shed small amounts of parasite eggs (24 sera) and (iii) an overlap area of both Fasciola species and where human shedding of parasite eggs in faeces is usually scarce or non‐existent (19 sera). One hundred and sixty‐eight patients with other parasitic infections and 89 healthy controls were also analysed. Results The respective sensitivity and specificity of this assay were 95.3% (95% confidence intervals, 82.9–99.2%) and 95.7% (95% confidence intervals, 92.3–97.5%). No correlation between egg output and the OD450 values of the F. hepatica IgG ELISA test was observed. Conclusions This test could be used both as an individual serodiagnostic test for human fascioliasis when backed up by a compatible clinical history together with a second diagnostic technique for other cross‐reactive helminth infections, and in large‐scale epidemiological studies of human fascioliasis worldwide. 相似文献