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101.
102.
In vitro parasiticidal effect of Nitazoxanide against Echinococcus multilocularis metacestodes 总被引:4,自引:0,他引:4
Stettler M Fink R Walker M Gottstein B Geary TG Rossignol JF Hemphill A 《Antimicrobial agents and chemotherapy》2003,47(2):467-474
When humans serve as inadvertent intermediate hosts for Echinococcus multilocularis, disease (alveolar echinococcosis [AE]) may result from the expanding parasite metacestode in visceral organs, mostly in the liver. Benzimidazole carbamate derivatives such as mebendazole and albendazole are used for chemotherapeutic treatment of AE. However, these treatments are, in most cases, parasitistatic rather than parasiticidal. As treatment is discontinued, a recurrence of parasite growth has been observed in many AE patients with nonradical resections. The only curative treatment for AE is radical surgical resection of the parasite tissue and support by chemotherapy. As there is a need for new treatment options for AE, the in vitro efficacy of nitazoxanide (NTZ), a broad-spectrum drug used against intestinal parasites and bacteria, was investigated. We showed that in vitro treatment of E. multilocularis metacestodes with NTZ induced high levels of alkaline phosphatase activity in the medium. Concurrently, distinct morphological and ultrastructural alterations were detected. Most significantly, two distinct types of alterations were observed as soon as after 3 h of NTZ treatment. At first, the drug induced a peripheral output of membranous vesicles from the tegumental membrane into the laminated layer. Simultaneously, germinal layer-associated undifferentiated cells produced large vacuoles filled with lipid-like and often electron-dense membranous segments. Other alterations were observed at later time points, including vacuolization of the germinal layer, accumulation of lipid droplets, and lastly, loss of microtriches and separation of the laminated and germinal layers. The pattern of damage induced by NTZ was different from the alterations earlier observed in albendazole sulfoxide-treated vesicles. The nonviability of NTZ-treated metacestodes was confirmed through bioassay, i.e., inoculation of treated and untreated parasites into mice. These experiments demonstrate the in vitro parasiticidal effect of NTZ on E. multilocularis metacestodes. 相似文献
103.
Lynn D Hawkins Sally T Ishizaka Pamela McGuinness Huiming Zhang Wendy Gavin Bruce DeCosta Zhaoyang Meng Hu Yang Maureen Mullarkey Donna W Young Hua Yang Daniel P Rossignol Anneliese Nault Jeffrey Rose Melinda Przetak Jesse C Chow Fabian Gusovsky 《The Journal of pharmacology and experimental therapeutics》2002,300(2):655-661
A series of novel, synthetic compounds containing lipids linked to a phosphate-containing acyclic backbone are shown to have similar biological properties to lipopolysaccharide (LPS). These compounds showed intrinsic agonistic properties when tested for their ability to stimulate tumor necrosis factor-alpha in human whole blood and interleukin-6 in U373 human glioblastoma cells without added LPS coreceptor CD14. The presence of the LPS antagonist E5564 completely blocked responses, suggesting that the novel compounds and LPS share a common mechanism of cell activation. Stereoselectivity of the molecules was observed in vitro; compounds with an R,R,R,R-configuration were strongly agonistic, whereas compounds with an R,S,S,R-configuration were much weaker in their activity on human whole blood and U373 cells. We also tested the effect of the compounds in cells transfected with the LPS receptor Toll-like receptor 4 (TLR4), with similar results, further supporting a shared mechanism with LPS. This was confirmed in vivo where the agonists failed to elicit cytokine responses in C3H/HeJ mice lacking TLR4 signaling. Because LPS-like molecules enhance immune responses, the compounds were mixed with tetanus toxoid and administered to mice in an immunization protocol to test for adjuvant activity. They enhanced the generation of specific antibodies against tetanus toxoid. Our results indicate that these unique compounds behave as agonists of TLR4, resulting in responses similar to those elicited by LPS. They display adjuvant activity in vivo and may be useful for the development of vaccine therapies. 相似文献
104.
Inflammatory bowel disease and the X chromosome 总被引:1,自引:0,他引:1
Hayward PA; Satsangi J; Jewell DP 《QJM : monthly journal of the Association of Physicians》1996,89(9):713-718
A review of documented cases demonstrates a significant association of
Turner's syndrome with Crohn's disease and ulcerative colitis; this
association relates particularly to genetic constitutions comprising an
abnormal rather than an absent X chromosome. The karyotype 46XiXq, in pure
or mosaic form, appears to be a significant susceptibility factor for
inflammatory bowel disease. This karyotype often gives rise to relatively
weak phenotypic characteristics of Turner's syndrome, which may be
overlooked in short females with inflammatory bowel disease. The
association of inflammatory bowel disease with Turner's syndrome may
reflect the presence on the X chromosome of genes involved in disease
pathogenesis. Linkage analysis studies, involving microsatellite markers on
the X chromosome, are being performed.
相似文献
105.
Little DM; Farrell JG; Cunningham PM; Hickey DP 《QJM : monthly journal of the Association of Physicians》1997,90(10):641-642
Systemic donor infection is regarded as being an absolute contraindication
to cadaveric organ donation for transplantation. This is largely due to
fear of transmitting pathogenic organisms to the immunosuppressed
recipient. However, due to the current shortage of organs available for
transplantation, clinicians are faced with the option of using organs from
'non-ideal' donors, such as those patients with documented evidence of
infection. We report the successful outcome of six orthotopic liver
transplants, 11 renal transplants, one combined heart lung transplant and
one simultaneous kidney and pancreas transplant with organs from eight
donors in whom bacterial meningitis (n = 7) and acute bacterial
epiglottitis (n = 1) were the antecedent causes of death.
相似文献
106.
107.
108.
Chronic inflammatory demyelinating polyneuropathy is a rare disease in pediatric patients. The disease usually responds well to standard therapies including immunoglobulins, corticosteroids, and plasmapheresis. However, a minority of cases appear refractory to standard treatments. This report presents the evolution of 13 patients with chronic inflammatory demyelinating polyneuropathy monitored in our pediatric neurology clinic between 1975 and 2005, including two recent patients with refractory diseases. The literature regarding treatment of refractory cases in adults and children is also reviewed. 相似文献
109.
110.
Rossignol S Barrière G Frigon A Barthélemy D Bouyer L Provencher J Leblond H Bernard G 《Brain Research Reviews》2008,57(1):228-240
The present paper reviews aspects of locomotor sensorimotor interactions by focussing on work performed in spinal cats. We provide a brief overview of spinal locomotion and describe the effects of various types of sensory deprivations (e.g. rhizotomies, and lesions of muscle and cutaneous nerves) to highlight the spinal neuroplasticity necessary for adapting to sensory loss. Recent work on plastic interactions between reflex pathways that could be responsible for such plasticity, in particular changes in proprioceptive and cutaneous pathways that occur during locomotor training of spinal cats, is discussed. Finally, we describe how stimulation of some sensory inputs via various limb manipulations or intraspinal electrical stimulation can affect the expression of spinal locomotion. We conclude that sensory inputs are critical not only for locomotion but also that changes in the efficacy of sensory transmission and in the interactions between sensory pathways could participate in the normalization of locomotion after spinal and/or peripheral lesions. 相似文献