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31.
32.
C K Hiebert W C Kopp H B Richerson C F Barfknecht 《Journal of medicinal chemistry》1983,26(12):1729-1732
A fluorescent-labeled muramyl dipeptide (MDP) has been prepared to probe immunoadjuvant cellular interactions. N-Acetylmuramyl-L-alanyl-D-isoglutamine (1) was synthesized in improved yield and reacted with 2-(fluoresceinylamino)-4,6-dichloro-s-triazine (DTAF, 2) to give the fluorescent adduct DTAF-MDP (3), attached through the 6-position of the sugar moiety. Adjuvant activity was assessed by using two different in vitro assays, macrophage spreading, and inhibition of macrophage migration. Both assays indicated that the apparent adjuvant activity of 3 is comparable to that of 1. 相似文献
33.
J J Seidenfeld D Wycoff D C Zavala H B Richerson 《British journal of industrial medicine》1978,35(3):245-257
An aerosol model for the study of paraquat (PQ) toxicity was developed using a 134 litre chamber and an ultrasonic nebuliser. Three groups of New Zealand white rabbits weighing 2-3 kg were studied. Group I (n = 6) was exposed to 10 g PQ/100 ml double-distilled water (DDW), Group II (n = 24) was exposed to 200 mg PQ/100 Ml DDW and a control group (n = 6) was exposed to 100 ml DDW. In a second experiment ten animals (Group III) were exposed to 10 mg PQ/100 ML DDW over a three-month period together with a control group (n = 5). Group I animals died with extensive haemorrhagic pneumonitis 38 hours after the last challenge. Most animals in Group II surviving more than three exposures had a significant reduction (P less than 0.001) in arterial oxygen tension (PaO2) and an increase (P less than 0.001) in the alveolar-arterial O2 gradient. Specific compliance decreased (P less than 0.005) and functional residual capacity and breathing frequency increased (P less than 0.05). Tissue PQ values showed even pulmonary distribution, with evidence of PQ accumulation after repeated inhalation. The lungs showed focal interstitial fibrosis, interstitial thickening, proliferation of macrophages in the alveoli, epithelioid changes in the interstitium, Type II cell hyperplasia, and foci of acute inflammation with consolidation. Controls and Group III animals were normal. This indicates that repeated inhalation of paraquat aerosol induces dose-related interstitial pneumonitis and fibrosis in rabbits. 相似文献
34.
Carrier requirement for development of acute experimental hypersensitivity pneumonitis in the rabbit
J E Butler H B Richerson P A Swanson M T Suelzer W C Kopp 《International archives of allergy and applied immunology》1983,71(1):74-82
Fluorescein isothiocyanate (FITC) conjugated to protein carriers was used to explore carrier dependence in an established rabbit model of acute hypersensitivity pneumonitis (HSP). Rabbits were immunized via toepads with either FITC-ovalbumin (OA) or FITC-human gamma-globulin (HGG) in complete Freund's adjuvant, and were aerosol challenged with homologous or heterologous conjugates 30 days later. Only those rabbits challenged with the homologous carrier developed acute HSP, despite the presence of comparable levels of anti-FITC antibodies in the sera of all groups. These findings indicate a strict carrier dependence in the pathogenesis of HSP in this model and provide further evidence that the mechanism of inflammation depends upon a cellular immune response. 相似文献
35.
36.
C K Hiebert W C Kopp H B Richerson C F Barfknecht 《Journal of medicinal chemistry》1988,31(10):2022-2024
Muramyl dipeptide (MDP) analogues were prepared and utilized in the synthesis of new fluorescently labeled MDP derivatives for use as biologic probes. Thus, N alpha-(N-acetylmuramyl)-L-lysyl-D-isoglutamine (Lys-MDP, 4) and N alpha-(N-acetylmuramyl)-L-alanyl-D-isoglutaminyl)-L-lysine [MTP, 5] were synthesized and then reacted with 2-(fluoresceinylamino)-4,6-dichloro-s-triazine (DTAF, 2) to yield the fluorescent adducts, DTAF-Lys-MDP (6) and DTAF-MTP (7). The adjuvant activity of the fluorescent MDP derivatives was determined by the ability of the compounds to promote delayed skin test responses in guinea pigs immunized with ovalbumin (OA) and by evaluating the anti-OA activity of these guinea pigs. 相似文献
37.
Chronic hypersensitivity pneumonitis produced in the rabbit by the adjuvant effect of inhaled muramyl dipeptide (MDP). 总被引:1,自引:0,他引:1 下载免费PDF全文
H. B. Richerson M. T. Suelzer P. A. Swanson J. E. Butler W. C. Kopp E. F. Rose 《The American journal of pathology》1982,106(3):409-420
An established rabbit model of acute hypersensitivity pneumonitis was used to evaluate adjuvant properties of synthetic muramyl dipeptide (MDP), the minimal adjuvant-active structure of mycobacteria. The authors studied MDP as a substitute for mycobacteria in immunization and as adjuvant during repeated inhalation of antigen (ovalbumin). They found that MDP could substitute successfully for mycobacteria in sensitizing animals for acute alveolitis following subsequent inhalation of a combination of ovalbumin and MDP aerosol for 4 to 14 weeks resulted in the development of chronic granulomatous pneumonitis, characterized by alveolar wall thickening, granulomas, and infiltrations with lymphocytes and macrophages. In addition, MDP boosted systemic and local IgG and IgA antigen-specific antibodies. Inhaled MDP, itself neither antigenic nor mitogenic, acted therefore as adjuvant for continued immunologic inflammatory effector mechanisms in the rabbit lung, which are ordinarily suppressed when antigen alone is inhaled. Possible mechanisms include stimulation of effector T cells and macrophages or the failure of suppressive mechanisms, with or without participation of immune complexes. This is the first successful model of chronic granulomatous alveolitis produced by inhalation of soluble materials. Further exploration of adjuvant mechanisms in this system should help clarify the pathogenesis of immunologic lung diseases in man. 相似文献
38.
人工牛黄是广泛用于中成药配方的中药代用品。本文用漫反射光谱法研究了人工牛黄样品在人工光源照射下发生颜色变化的光解规律:在三种光源下,其光解均属二步表观一级反应动力学,即光解曲线是由两段斜率不同的直线组成,初期的光解速度较其后的快2倍左右;不同光源下,紫外灯光解速度最快,荧光高压汞灯次之,碘钨灯最慢;表观光解常数与光波长有关,但基本不随光强度和照射时间乘积改变。而光解时间则与光强度成反比。从得到的动力学方程可预测不同条件下的褪色时间。研究表明,人工牛黄复方中,发生光解的主要成分是胆红素,其余成分不发生引起颜色变化的光解,但在第二步反应中对胆红素的光解有明显影响。 相似文献
39.
Pathogenesis of shigella diarrhea. VII. Evidence for a cell membrane toxin receptor involving β1 {arrow} 4-linked N-acetyl-D-glucosamine oligomers 总被引:1,自引:0,他引:1 下载免费PDF全文
The binding of ShigeUa dysenteriae 1 cytotoxin to HeLa cells in culture and to isolated rat liver cell membranes was studied by means of an indirect consumption assay of toxicity from the medium, or by determination of cytotoxicity to the HeLa cell monolayer. Both liver cell membranes and HeLa cells removed toxicity from the medium during incubation, in contrast to WI-38 and Y-1 mouse adrenal tumor cells, both of which neither bound nor were affected by the toxin. Uptake of toxin was directly related to concentration of membranes added, time,and temperature, and indirectly related to the ionic strength of the buffer used. The chemical nature of the membrane receptor was characterized by using three principal approaches: (a) enzymatic sensitivity; (b) competitive inhibition and (c) receptor blockade studies. The receptor was destroyed by proteolytic enzymes, phospholipases (which markedly altered the gross appearance of the membrane preparation) and by lysozyme, but not by a variety of other enzymes. Of 28 carbohydrate and glycoprotein haptens studied, including cholera toxin and ganglioside, only the chitin oligosaccharide lysozyme substrates, per N-acetylated chitotriose, chitotetraose, and chitopentaose were effective competitive inhibitors. Greatest inhibition was found with the trimer, N, N’, N” triacetyl chitotriose. Of three lectins studied as possible receptor blockers, including phytohemagglutinin, concanavalin A, and wheat germ agglutinin, only the latter, which is known to possess specific binding affinity for N, N’, N” triacetyl chitotriose, was able to block toxin uptake. Evidence from all three approaches indicate, therefore, existence of a glycoprotein toxin receptor on mammalian cells, with involvement of oligomeric β1{arrow}4-1inked N-acetyl glucosamine in the receptor. This receptor is clearly distinct from the G(M1) ganglioside thought to be involved in the binding of cholera toxin to the cell membrane of a variety of cell types susceptible to its action. 相似文献
40.