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41.
U. Abshagen H. Rennekamp G. Luszpinski 《Naunyn-Schmiedeberg's archives of pharmacology》1976,296(1):37-45
Summary Five healthy male volunteers received 500 mg Aldactone® orally together with 100 Ci 3H-20-21-spironolactone; one elderly patient received 1 mCi 3H-spironolactone without additional cold drug. For 6 days the disposition kinetics of the drug were studied in plasma, urine and feces. The tritium concentrations in plasma reached a peak between 25–40 min after administration amounting to 2–3% of the dose/1. Up to the 12th h, they fell rapidly and showed a monoexponential decline (t
1/2
: 2.57±0.27 days) between the 36th and 96th h. Later, a striking increase in the speed of elimination of radioactivity from plasma (t
1/2
: 1.66±0.21 days) was observed. The biological half-life of labeled material in plasma was longer than that of fluorigenic compounds. 47–57% of the dose were excreted in urine and the remaining amount culd be detected in feces (total recovery 90%). The half-life of the urinary excretion rate was distinctly shorter (t
1/2
: 0.9±0.11 days) than that of total radioactivity in plasma. This, together with an observed increase of the polar fraction in urine from 35 up to 85%, which was accompanied by a decrease in plasma from 55 to 35%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. TLC-separation of the lipophilic fraction in urine revealed two previously unknown compounds of which the main congener was identified as 3-(3-oxo-7-methylsulfonyl-6, 17-dihydroxy-4-androsten-17-yl) propionic acid -lactone, as well as canrenone and the metabolites which have already been described (Karim and Brown, 1972; Karim et al., 1975). This metabolite represents the main lipophilic degradation product in urine within the first hours, whereas the 6-OH-7-methylsulfinylspirolactone leveled off and seemed to be an endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.The paper includes parts of the thesis of G. Luszpinski 相似文献
42.
m-Dinitrobenzene intoxication due to skin absorption 总被引:1,自引:0,他引:1
Nobuo Ishihara Akira Kanaya Masayuki Ikeda 《International archives of occupational and environmental health》1976,36(3):161-168
Summary A case of m-dinitrobenzene intoxication is described. Clinical picture of the patient who was exposed to an industrial material containing m-dinitrobenzene, methaemoglobinemia and excretion of urinary metabolites observed in a volunteer who experimentally worked with the same material, absence of m-dinitrobenzene in the ambient air during the exposure, and penetration of m-dinitrobenzene through the protective gloves which were used by the patient indicate that m-dinitrobenzene was the toxic agent and that the main route of the invasion was skin absorption. 相似文献
43.
Study on Metabolites of Aconitum Alkaloids in Human Urine 总被引:1,自引:0,他引:1
ForMaster‘sDegree:SUNYing Supervisor:Prof.ZHANGHong-gui ZHONGda-fang ZHANGHan-qi 《中国药学》2003,12(1):54-55
TheaconitebelongstoplantsofgenusAconituminfamilyofRanunculaceaandhavenotableclinicalfunctionsintreatingrheumaticarthritis ,heartfailure ,etc .However,accidentsofaconitine(fromaconite)poisoningfrequentlyoccurtomanypeopletakingtheseherbs .Theplantsofthisfamilycontainaconitine ,mesaconitine ,hypaconitineandotheraco nitumalkaloids .Theyarehighlytoxic ,andtheirtreatmentdoseapproachestothetoxicdoseorlethaldose .Duringtheperiodfrom 1989- 1995 ,morethan 30casesofpoisoningcausedbyaconitineinsometradit… 相似文献
44.
2-Methoxyestradiol (2-MeO-E2), a major metabolite of 17β-estradiol, may function as a physiological tumor suppressor and is being investigated for clinical
applications. It has been reported to target rapidly dividing cells. We investigated the effects of 2-MeO-E2 on the growth plate of young rats because normal longitudinal bone growth requires rapid proliferation of cartilage and endothelial
cells. Sexually mature (3-month-old) normal female rats were treated with 2-MeO-E2 (100 mg/kg/day) for 13 days and it was found to have no effect on uterine weight but reduced serum cholesterol. The estrogen
metabolite had no effect on either cortical or cancellous bone. In contrast, 2-MeO-E2 dramatically reduced longitudinal bone growth rate at the proximal tibia from 55 ± 2 to 20 ± 2 μm/day (P < 0.001) and growth plate thickness from 153 ± 14 to 70 ± 6 μm (P < 0.001). The latter decrease was due to significant reductions in the height of both the proliferative (P < 0.001) and the hypertrophic (P < 0.001) zones. These results in normal female rats demonstrate that 2-MeO-E2 inhibited longitudinal bone growth but had no effect on either radial bone growth or cancellous bone turnover. 2-MeO-E2 was shown by these studies to have the ability to discriminate between bone and cartilage, as well as between reproductive
and nonreproductive estrogen-target tissues. Thus, 2-MeO-E2 is a naturally produced estrogen metabolite that demonstrates unique tissue selectivity.
Received: 21 July 1999 / Accepted: 12 January 2000 相似文献
45.
目的: 建立人单核巨噬细胞泡沫化抑制剂筛选模型,筛选得到可抑制细胞泡沫化的抑制剂.方法: U937单核细胞经100 nmol·L-1佛波酯(PMA)诱导72 h分化为巨噬细胞后,换无血清培养液于96孔板中,每毫升含巨噬细胞1×106个,每孔再加入80 mg·L-1氧化的低密度脂蛋白(ox-LDL),37 ℃培养48 h,建立单核巨噬细胞泡沫化模型.利用微生物发酵液,或单一的化合物样品与其共孵育,油红.染色后观察细胞胞内变化,寻找对泡沫细胞形成有抑制作用的样品.利用基因工程技术表达的人清道夫受体A类II型的胞外部分,在本模型中可抑制巨噬细胞泡沫化的形成,进一步验证了模型的可行性.结果: 从2000 个微生物发酵液中筛选到6株微生物发酵液为阳性,从10个化合物中发现一个有抑制巨噬细胞泡沫化活性的新化合物.结论: 本模型可用于细胞泡沫化抑制剂的高通量筛选. 相似文献
46.
BACKGROUND: In spite of its high placental transfer, propofol is frequently used in general anesthesia and sedation during obstetric and gynecological surgery such as in vitro fertilization. This study investigated whether or not propofol has a genotoxic potential by the sister chromatid exchange assay in vitro. METHODS: Sister chromatid exchanges induced after exposure to propofol were measured in Chinese hamster ovary cells with and without metabolic activation. After propofol (0.2-20 microg ml(-1)) diluted dimethyl sulfoxide was applied for 2 h with or without S9 mix, the cells having been incubated for two metaphases (34 h) in the presence of 5'-bromo-2-deoxyuridine. N-nitrosodimethylamine and mitomycin C were used as positive controls with and without metabolic activation. The chromosomes were stained with the fluorescence plus Giemsa method, and then sister chromatid exchanges in 50 cells were counted for each concentration. RESULTS: Although increasing concentrations of propofol inhibited cell proliferation, no concentrations of propofol used in this study increased the sister chromatid exchange values, with and without metabolic activation. CONCLUSION: It was concluded that there was no indication, from the sister chromatid exchange assay in mammalian cells, of a genotoxic effect of propofol and its metabolites. 相似文献
47.
海洋来源的放线菌次级代谢产物及其生物活性 总被引:7,自引:0,他引:7
放线菌是迄今最重要和最大的药用微生物种群。海洋放线茵生存于苛刻特殊的海洋环境,使其具备了复杂独特的代谢途径,其次级代谢产物在结构类型以及在生物活性等方面都呈现出与陆生放线茵不同的特点和多样性。多年来,诸多结构新颖、生物活性显著的天然活性产物持续从海洋来源放线茵代谢产物中被发现,这些活性化合物为新药研究提供了丰富的先导化合物,有些已进入研发阶段。近年,海洋放线茵活性产物的研究仍然是海洋微生物产物研究中值得关注的一个热点。本文按化舍物结构类型简要介绍了海洋来源放线茵代谢产物及其生物活性的研究概况。 相似文献
48.
目的研究鉴定丁香酚布洛芬酯在大鼠体内的代谢行为。方法选择健康Wistar大鼠3只单剂量20mg·kg-1尾静脉给药丁香酚布洛芬酯后,收集0~12h尿样。将尿样经SPEC18固相萃取柱纯化后,采用LC/MSn方法对尿中的待测的代谢产物进行选择离子监测(SIM)和多级全扫描质谱分析(MSn)。结果在尿中首次检测到丁香酚布洛芬酯的7种代谢产物,其中包括1种Ⅰ相代谢产物和6种Ⅱ相代谢产物。结论丁香酚布洛芬酯在大鼠体内主要先水解成丁香酚和布洛芬,经进一步代谢与葡萄糖醛酸结合。 相似文献
49.
头孢霉AL031真菌次生代谢产物的抗菌活性研究 总被引:1,自引:0,他引:1
采用滤纸片法 ,以 11株革兰氏阳性或阴性细菌为指示菌 ,对从头孢霉AL0 31真菌次生代谢产物中分离到的 14个化合物进行了体外抗细菌活性筛选。结果表明 :新化合物 :S ( ) 5 羟基蜂蜜曲菌素、S ( ) 7 羟基蜂蜜曲菌素和已知化合物 :蜂蜜曲菌素、2 ,4 -二羟基 3,6 二甲基苯甲酸、3,6 二羟基 2 ,4 二甲基苯甲酸、琥珀酸具有广谱的抗细菌活性 ,采用杯碟法 ,以三种细菌为指示菌 ,测定了具有抗菌活性的 6个化合物的最低抑菌浓度 (MIC) ,其MIC为 0 0 312 5~ 0 5mg/ml。 相似文献
50.
《International journal of hygiene and environmental health》2014,217(2-3):421-426
DINCH (diisononylcyclohexane-1,2-dicarboxylate) was introduced into the world market in 2002 as a non-aromatic plasticizer and phthalate substitute. We analyzed 300 urine samples (24 h voids) of the German Environmental Specimen Bank (ESB for Human tissues, ESB Hum) for specific DINCH metabolites by on-line HPLC–MS/MS with isotope dilution quantification. Urine samples of the ESB Hum were from the years 1999, 2003, 2006, 2009 and 2012, chosen to investigate the appearance and a possible trend of DINCH exposure since its market introduction. No DINCH metabolites were detected in the 1999 and 2003 samples. From 2006 on, the percentage of samples with DINCH metabolites above the LOQ increased significantly over the years (7% in 2006, 43% in 2009 and 98% in 2012). The cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (OH-MINCH) was the predominant metabolite. Median (and 95th percentile) concentrations (in μg/l) increased from <LOQ (0.09) in 2006, to <LOQ (1.02) in 2009 to 0.39 (2.09) in 2012. All oxidized DINCH metabolites (OH-MINCH, cx-MINCH, oxo-MINCH) correlated strongly among each other (ρ > 0.75, p < 0.001). The median (95th percentile) DINCH intake in 2012 was calculated to be 0.14 (1.07) μg/kg body weight/day which is considerably below daily intakes currently deemed tolerable. DINCH is regarded to have a preferred toxicological profile over certain anti-androgenic phthalates. The continuation of DINCH measurements in the ESB Hum and other human biomonitoring studies like the German Environmental Survey (GerES) allows tracking the development of DINCH body burdens, the distribution of exposure levels and daily intakes, providing basic data for future toxicological assessment and further epidemiological studies. 相似文献