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91.
Gene Expression Profiles in Zebrafish Brain after Acute Exposure to Domoic Acid at Symptomatic and Asymptomatic Doses 总被引:1,自引:0,他引:1
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Kummar S Copur MS Rose M Wadler S Stephenson J O'Rourke M Brenckman W Tilton R Liu SH Jiang Z Su T Cheng YC Chu E 《Clinical colorectal cancer》2011,10(2):85-96
PHY906 is a novel Chinese herbal preparation that has been used in the Orient for over 1800 years to treat a wide range of gastrointestinal side effects including diarrhea, abdominal cramps, vomiting, fever, and headache. Preclinical and clinical studies were conducted to further investigate the biologic and clinical activities of this herbal medicine. To ensure standardization and maintain interbatch reliability of PHY906, high performance liquid chromatography (HPLC) was used to establish a "chemical fingerprint" of PHY906. In vivo preclinical studies using the murine Colon 39 tumor model showed that PHY906 protected against the weight loss associated with irinotecan treatment. In the presence of PHY906, mice were able to tolerate otherwise lethal doses of irinotecan. Significantly improved antitumor activity and overall survival were observed in animals treated with the combination of irinotecan and PHY906 versus irinotecan alone. The combination of PHY906 with irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV) also resulted in at least additive antitumor activity with no increased host toxicity. Based on these in vivo studies, a phase I multicenter, double-blind, randomized, placebo-controlled, dose escalation, cross-over study of PHY906 as a modulator of the weekly, bolus regimen of irinotecan, 5-FU, and LV (IFL) in the first-line treatment of patients with advanced colorectal cancer (CRC) was conducted. The specific objectives of this clinical trial were to determine the safety and tolerability of PHY906 when administered concomitantly with the bolus, weekly IFL regimen. Treatment with PHY906 did not alter the pharmacokinetics of 5-FU, irinotecan, or the irinotecan metabolite SN-38. 相似文献
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Increasingly, pharmaceutical and biotech companies have begun to realize the importance of obtaining solubility information in early drug discovery as it is one of the critical parameters for lead selection and optimization. This report introduces a high-throughput equilibrium solubility (HT-Eq sol) assay using a novel miniaturized shake-flask approach and streamlined HPLC analysis. The new HT-Eq sol assay, validated and optimized via a test set of 85 marketed drugs and Novartis internal compounds, shows an excellent correlation to the conventional shake-flask thermodynamic solubility data generated in-house and the equilibrium solubility results reported in literature. It therefore offers a fast, reliable and cost-effective screening tool for solubility assessment in early drug discovery, allowing for prioritization of drug candidates using aqueous solubility in conjunction with other profiling information and efficacy data. Our work demonstrates that presence of a small amount of DMSO (0.5-5%) will result in significant overstimation of equilibrium solubility (up to 6 folds). In addition, monitoring of drug dissolution process using the current approach as well as the interplay between equilibrium solubility data and those from kinetic solubility are discussed. 相似文献
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Normal and stenotic renal arteries: experimental balloon-expandable intraluminal stenting 总被引:2,自引:0,他引:2
Palmaz JC; Kopp DT; Hayashi H; Schatz RA; Hunter G; Tio FO; Garcia O; Alvarado R; Rees C; Thomas SC 《Radiology》1987,164(3):705-708
Elastic recoil of the vessel wall is a common cause of failure of percutaneous transluminal angioplasty in renal arteries. To oppose such recoil, balloon-expandable metal stents were implanted in artificially stenotic renal arteries in pigs and normal renal arteries in dogs and pigs. The stents were then examined angiographically and histologically at regular intervals. All stents were completely covered with endothelialized neointima in 3 weeks. There was no difference in intimal thickness between the stenotic and nonstenotic renal arteries. A large stent diameter and a large open or nonmetal surface may cause less intimal hyperplasia, but nonturbulent, fast arterial flow is probably the most important factor in ensuring long-term patency of the vessel. 相似文献
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Rudy W; Guckel B; Siebels M; Lindauer M; Meuer SC; Moebius U 《International immunology》1997,9(6):853-860
Introduction of co-stimulatory molecules like CD80 and CD86 represents a
means to augment the immunogenicity of tumor cells and to induce immune
responses directed at tumor antigens. Here we compared CD80- and
CD86-transfected human melanoma cells to induce primary immune responses by
their capacity to promote proliferation of human allogeneic resting T
lymphocytes. CD80- and CD86-transfected SkMel63 melanoma cells induced T
cell activation to a comparable degree, which was found to be independent
of the cell surface density of these co- stimulatory molecules.
Co-expression of CD80 and CD86 did not result in a synergistic increase in
T cell proliferation. Both CD80 and CD86 transfectants induced the
proliferation of isolated CD4+ or CD8+ T cells. Exogenous IL-2, IL-4 and
tumor necrosis factor-alpha respectively enhanced primary T cell
proliferation independent of CD80 or CD86 expression. Interestingly,
differential activities of CD80 and CD86 were observed following
stimulation of resting T cells in the presence of IL-12. Whereas IL-12
increased T cell proliferation in the presence of CD86-transfected melanoma
cells, it exhibited an inhibitory function in the presence of
CD80-expressing SkMel63 cells. Experimental evidence indicates that this
inhibitory effect was mediated by IFN- gamma since (I) IFN-gamma secretion
of stimulated T cells was augmented by IL-12, (II) exogenous IFN-gamma also
inhibited T cell proliferation induced by CD80- but not CD86-transfected
SkMel63 cells and (III) the inhibitory effect of IL-12 was blocked by an
anti-IFN-gamma mAb.
相似文献
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