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101.
102.
D Green S Santhanam F A Krumlovsky F del Greco 《The Journal of laboratory and clinical medicine》1980,95(5):679-685
Elevated plasma concentrations of beta-thromboglobulin were observed in 25 consecutive patients with chronic renal failure. Further increases in this platelet protein were observed during hemodialysis but not during peritoneal dialysis. The hemodialysis-induced increases were not prevented by either aspirin or dipyridamole, a fact which suggested that release of this protein was not dependent on platelet functional activity. Measurement of beta-thromboglobulin provides a sensitive indicator of platelet disruption during hemodialysis. 相似文献
103.
Trotta R Ciarlariello D Dal Col J Allard J Neviani P Santhanam R Mao H Becknell B Yu J Ferketich AK Thomas B Modi A Blaser BW Perrotti D Caligiuri MA 《The Journal of experimental medicine》2007,204(10):2397-2405
Monokines (i.e., interleukin [IL]-12, -18, and -15) induce natural killer (NK) cells to produce interferon-gamma (IFN-gamma), which is a critical factor for immune surveillance of cancer and monocyte clearance of infection. We show that SET, which is a potent inhibitor of protein phosphatase type 2A (PP2A) activity, is highly expressed in human CD56bright NK cells, which produce more IFN-gamma than CD56dim NK cells. SET was up-regulated upon monokine stimulation of primary human NK cells. Furthermore, ectopic overexpression of SET significantly enhanced IFN-gamma gene expression in monokine-stimulated NK cells. In contrast, RNAi-mediated suppression of SET expression renders NK cells inefficient in producing high levels of IFN-gamma in response to monokine costimulation. Mechanistically, suppression of PP2A activity by SET is important for IFN-gamma gene expression in NK cells. In fact, treatment of primary human NK cells with the PP2A activator 1,9-dideoxy-forskolin, as well as administration of the drug to C57BL/6 mice, significantly reduced NK-dependent IFN-gamma production in response to monokine treatment. Further, SET knockdown or pharmacologic activation of PP2A diminished extracellular signal-regulated kinase 1/2, p65RelA, signal transducer and activator of transduction 4 (STAT4), and STAT5 activity in monokine-stimulated NK cells, potentially contributing to the reduction in IFN-gamma gene expression. Thus, SET expression is essential for suppressing PP2A phosphatase activity that would otherwise limit NK cell antitumoral and/or antiinflammatory functions by impairing NK cell production of IFN-gamma. 相似文献
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Salas A Ponnusamy S Senkal CE Meyers-Needham M Selvam SP Saddoughi SA Apohan E Sentelle RD Smith C Gault CR Obeid LM El-Shewy HM Oaks J Santhanam R Marcucci G Baran Y Mahajan S Fernandes D Stuart R Perrotti D Ogretmen B 《Blood》2011,117(22):5941-5952
The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances Bcr-Abl1 protein stability, through inhibition of its proteasomal degradation in imatinib-resistant K562/IMA-3 and LAMA-4/IMA human CML cells. In fact, Bcr-Abl1 stability was enhanced by ectopic SK-1 expression. Conversely, siRNA-mediated SK-1 knockdown in K562/IMA-3 cells, or its genetic loss in SK-1(-/-) MEFs, significantly reduced Bcr-Abl1 stability. Regulation of Bcr-Abl1 by SK-1/S1P was dependent on S1P receptor 2 (S1P2) signaling, which prevented Bcr-Abl1 dephosphorylation, and degradation via inhibition of PP2A. Molecular or pharmacologic interference with SK-1/S1P2 restored PP2A-dependent Bcr-Abl1 dephosphorylation, and enhanced imatinib- or nilotinib-induced growth inhibition in primary CD34(+) mononuclear cells obtained from chronic phase and blast crisis CML patients, K562/IMA-3 or LAMA4/IMA cells, and 32Dcl3 murine progenitor cells, expressing the wild-type or mutant (Y253H or T315I) Bcr-Abl1 in situ. Accordingly, impaired SK-1/S1P2 signaling enhanced the growth-inhibitory effects of nilotinib against 32D/T315I-Bcr-Abl1-derived mouse allografts. Since SK-1/S1P/S1P2 signaling regulates Bcr-Abl1 stability via modulation of PP2A, inhibition of SK-1/S1P2 axis represents a novel approach to target wild-type- or mutant-Bcr-Abl1 thereby overcoming drug resistance. 相似文献
107.
Saleem TF Santhanam P Hamoudeh E Hassan T Faiz S 《The West Virginia medical journal》2012,108(2):26-30
We are presenting the clinical features, diagnostic work up and treatment of acromegaly caused by Growth hormone releasing hormone (GHRH) secreting neuroendocrine tumor (NECT) in a case of multiple endocrine neoplasia type 1 (MEN-1). A 36 year old man, known case of MEN-1 presented with acromegalic features. He has high IGF-1, GH and very high GHRH levels with a pancreatic head tumor and pituitary mass. He had high GHRH arteriovenous gradient across pancreatic tumor and underwent tumor resection, Post operative GHRH level fell dramatically. Tumor had high GHRH m-RNA level. Acromegalic patients with MEN-1 should be screened for ectopic GHRH secretion. Measurement of GHRH arteriovenous gradient across NECT or mRNA for GHRH in resected tumor can confirm the ectopic source. Treatment of choice is surgical resection of the tumor. Somatostatin analogue is an alternative because of its dual action in the pituitary gland and the NECT. Life long surveillance is needed as recurrence chance is high. 相似文献
108.
Santhanam AP Min Y Neelakkantan H Papp N Meeks SL Kupelian PA 《International journal of computer assisted radiology and surgery》2012,7(5):705-719
Purpose
Medical simulation frameworks facilitate both the preoperative and postoperative analysis of the patient??s pathophysical condition. Of particular importance is the simulation of radiation dose delivery for real-time radiotherapy monitoring and retrospective analyses of the patient??s treatment.Methods
In this paper, a software framework tailored for the development of simulation-based real-time radiation dose monitoring medical applications is discussed. A multi-GPU-based computational framework coupled with inter-process communication methods is introduced for simulating the radiation dose delivery on a deformable 3D volumetric lung model and its real-time visualization. The model deformation and the corresponding dose calculation are allocated among the GPUs in a task-specific manner and is performed in a pipelined manner. Radiation dose calculations are computed on two different GPU hardware architectures. The integration of this computational framework with a front-end software layer and back-end patient database repository is also discussed.Results
Real-time simulation of the dose delivered is achieved at once every 120?ms using the proposed framework. With a linear increase in the number of GPU cores, the computational time of the simulation was linearly decreased. The inter-process communication time also improved with an increase in the hardware memory. Variations in the delivered dose and computational speedup for variations in the data dimensions are investigated using D70 and D90 as well as gEUD as metrics for a set of 14 patients. Computational speed-up increased with an increase in the beam dimensions when compared with a CPU-based commercial software while the error in the dose calculation was <1%.Conclusion
Our analyses show that the framework applied to deformable lung model-based radiotherapy is an effective tool for performing both real-time and retrospective analyses. 相似文献109.
110.
Poor post-natal growth of preterm neonates is common and fortification is recommended. However, this is not always practical in low-resource areas. Hypothesizing that increasing the volume of feeds would be safe and lead to better post-natal weight gain, we randomized 64 babies with birth weight <1500?g, once they reached full feeds, to continue feeds at 200?ml/kg/day (standard volume) or increase to 300?ml/kg/day (high volume) of expressed breast milk. There was a significantly higher daily weight gain in the high-volume group as compared to the standard volume group (24.9 vs. 18.7?g/kg/day, p?0.0001). There were no differences in complications like feed intolerance, tachypnoea, sepsis, patent ductus arteriosus or necrotizing enterocolitis. High-volume feeds at 300?ml/kg/day was safe and resulted in better weight gain than standard volume feeds in very low birth weight babies. 相似文献