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51.
David Fange Karin Nilsson Tanel Tenson M?ns Ehrenberg 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(20):8215-8220
Recent experiments have shown that drug efflux pump deficiency not only increases the susceptibility of pathogens to antibiotics, but also seems to “mask” the effects of mutations, that decrease the affinities of drugs to their intracellular targets, on the growth rates of drug-exposed bacteria. That is, in the presence of drugs, the growth rates of drug-exposed WT and target mutated strains are the same in a drug efflux pump deficient background, but the mutants grow faster than WT in a drug efflux pump proficient background. Here, we explain the mechanism of target resistance masking and show that it occurs in response to drug efflux pump inhibition among pathogens with high-affinity drug binding targets, low cell-membrane drug-permeability and insignificant intracellular drug degradation. We demonstrate that target resistance masking is fundamentally linked to growth-bistability, i.e., the existence of 2 different steady state growth rates for one and the same drug concentration in the growth medium. We speculate that target resistance masking provides a hitherto unknown mechanism for slowing down the evolution of target resistance among pathogens. 相似文献
52.
Kathryn K. Collins George F. Van Hare Naomi J. Kertesz Ian H. Law Yaniv Bar-Cohen Anne M. Dubin Susan P. Etheridge Charles I. Berul Jennifer N. Avari Volkan Tuzcu Narayanswami Sreeram Michael S. Schaffer Anne Fournier Shubhayan Sanatani Christopher S. Snyder Richard T. Smith Jr Luis Arabia Robert Hamilton Terrence Chun Leonardo Liberman Bahram Kakavand Thomas Paul Ronn E. Tanel 《Journal of the American College of Cardiology》2009
53.
Tissue levels,histologic changes and plasma pharmacokinetics of meta-Tetra (hydroxyphenyl) chlorin (mTHPC) in the cat 总被引:1,自引:0,他引:1
Campbell GA Bartels KE Arnold C Healey T Cowell RL Lucroy MD Ronn AM 《Lasers in medical science》2002,17(2):79-85
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The biodistribution and pharmacokinetics of meta-tetra(hydroxyphenyl)chlorin (mTHPC)1 have been documented in humans, rats, dogs and rabbits. It has been demonstrated to be an effective photodynamic therapy
agent for treatment of squamous cell carcinoma. Squamous cell carcinoma is a common feline neoplasm, causing significant morbidity
and mortality in the feline population. The association between ultraviolet radiation exposure and occurrence of this neoplasm
in the cat provides a useful model for the study of human cutaneous squamous cell carcinoma. In this study, we document the
biodistribution, pharmacokinetics and toxicity of mTHPC in a group of normal cats. Four groups of cats were given the drug
intravenously at dosages of 0, 0.15, 0.30 and 0.60 mg/kg. mTHPC levels were measured in plasma and tissues at 0, 24, 48, 72,
96 and 336 h after drug administration. Additionally, plasma samples were collected at 1 and 6 h post-injection and analysed.
Biodistribution and pharmacokinetics of mTHPC in cats mirrors that in other animal species. There were no clinical or pathological
changes associated with administration of the drug. The biodistribution and pharmacokinetics of mTHPC in cats mirrors that
in other species studied. There were no clinical or pathological changes attributable to administration of the drug at the
doses administered. mTHPC may be a useful photodynamic therapy drug in cats.
Paper received 15 June 2001; accepted after revision 5 September 2001. 相似文献
54.
The serum prostate specific antigen (PSA), having been a valid marker for prostate cancer in 2 patients at the time of their diagnosis, ultimately became undetectable (<0.1 ng/ml) despite evidence of disease progression. This was documented by isotope bone scans and the results of subsequent CT guided bone biopsies. In both biopsy specimens, immunohistochemical staining for PSA was negative, but positive for prostate acid phosphatase after microwave antigen enhancement. In both cases the serum prostate acid phosphatase (PAP) had remained within normal limits. We would caution that prostate cancer may recur and progress with an undetectable serum PSA after antiandrogen therapy. 相似文献
55.
Tanel Traks Kati Koido Triin Eller Eduard Maron Külli Kingo Veiko Vasar Eero Vasar Sulev Kõks 《BMC medical genetics》2008,9(1):111
Background
Innate immune inflammatory response is suggested to have a role in the pathogenesis of major depressive disorder (MDD). Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20, and IL-24 are all implicated in the inflammatory processes and polymorphisms in respective genes have been associated with various immunopathological conditions. This study was carried out to investigate whether single-nucleotide polymorphisms (SNPs) in these genes are also associated with MDD. 相似文献56.
Latent infection induced with cottontail rabbit papillomavirus. A model for human papillomavirus latency. 总被引:3,自引:0,他引:3 下载免费PDF全文
C. A. Amella L. A. Lofgren A. M. Ronn M. Nouri M. J. Shikowitz B. M. Steinberg 《The American journal of pathology》1994,144(6):1167-1171
Latent human papillomavirus infection, a very common event, is most likely the source of primary and recurrent papillomas of the respiratory and genital tracts and might also be the source of neoplastic lesions of the female genital tract and the penis. We have developed a simple model for papillomavirus latency using cottontail rabbit papillomavirus. Skin of domestic rabbits was minimally scarified and inoculated with dilutions of a crude virus suspension ranging from 200 ng to 20 pg viral DNA per inoculated site. Dilution of virus to less than 10 ng/site resulted in delayed and reduced efficiency of inducing warts. After follow-up of 1 to 6 months, sites immediately adjacent to papillomas and inoculated sites where papillomas did not form were biopsied and analyzed by Southern blot and polymerase chain reaction. Inoculated tissues that were clinically and histologically normal contained viral DNA at low levels, detectable by polymerase chain reaction. Ability of the latent virus to induce warts was confirmed by activation with mild skin irritation causing wart formation. This simple model system for latent papillomavirus can be used to study mechanisms of viral activation, therapies to prevent activation, and therapies to eliminate latent virus and thus cure the infection. 相似文献
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