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1.
Nine healthy subjects received 0.2 mg of beta-methyldigoxin (beta-MD) orally in the fasting state, 30 minutes after and before a standard breakfast. The time-to-peak serum glycoside concentration was delayed and the peak concentration was lower in the postprandial state compared with the other regimens (P less than .01). The absorption rate constant was significantly reduced when beta-MD was given after a meal (1.55 +/- 1.75 hr-1) than before a meal (5.54 +/- 2.16 hr-1) and in the fasting state (5.22 +/- 3.06 hr-1)(P less than .01). Although the area under the serum glycoside concentration-time curve and the cumulative urinary excretion (CUE) of beta-MD, digoxin, and total drug (beta-MD plus digoxin) was not significantly different between three regimens, the CUE infinity tended to be smaller in the postprandial state compared with before a meal. The results indicate that the timing of drug administration in relation to a meal is an important factor leading to the fluctuations of serum glycoside concentration after oral beta-MD, which might be of some clinical importance. 相似文献
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An attempt was made to detect a pancreatic tumor antigen (PTA) in transplantable pancreatic adenocarcinomas induced by N-bis(2-hydroxypropyl)nitrosamine (DHPN) in hamsters. Antibody against antigenic protein was raised by immunizing rabbits with whole homogenate of the tumors transplanted into the back of hamsters. PTA was purified by affinity chromatography and shown to have the physicochemical properties of a glycoprotein with a molecular weight of 800,000, migrating in the beta regions upon agarose gel electrophoresis. Loss of immunological properties was observed after heating at 65 degrees C for 30 min. Enzyme immunoassay revealed that the levels of PTA in the serum and tissue showed a positive correlation with the induction of the presence of tumor, and size of the tumor. It is tentatively suggested that PTA values above 150 ng/ml serum are indicators of tumors, because in normal hamsters the PTA range is from 25 to 130 ng/ml serum. Immunohistochemically, PTA was demonstrated to be localized within the cytoplasm of epithelial tumor cells of well-differentiated tubular adenocarcinomas. 相似文献
4.
Yamamoto Kazuhiko; Nakajima Akira; Eimoto Hiroyuki; Tsutsumi Masahiro; Maruyama Hiroshi; Denda Ayumi; Nii Hiroaki; Mori Yukio; Konishi Yoichi 《Carcinogenesis》1989,10(9):1607-1611
The carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine(BHP) was investigated in male Wistar rats administered bis(2-hydroxypropyl)amine(BHPA) mixed in powder diet at a concentration of 1%, and sodiumnitrite (SN) dissolved in distilled water at concentrationsof 0.15 and 0.3%, for 94 weeks. Urinary excretion of BHP wasdetected in rats given 1% BHPA and 0.3% SN but not in the groupsreceiving either of these precursors alone. Nasal cavity, lung,esophagus, liver and urinary bladder tumors were found in animalstreated with combinations of 1% BHPA and 0.15 or 0.3% SN, suggestingthat the target organs of the endogenously synthesized BHP aresimilar to those affected when the carcinogen is administeredexogenously. The incidences of nasal cavity and lung tumorsreached 74 and 58% in rats given 1% BHPA and 0.3% SN, respectively.Tumors at sites other than target organs were only found atlevels similar to those previously reported for spontaneoustumors in male Wistars. The present results clearly indicatedthe tumor inducibility of a nhrosatable amine, BHA, throughan endogenous nitrosation by feeding to rats in conjunctionwith nitrite, and provide further suggestive evidence that endogenousnitrosations of environmental nitrosatable amines can be a potentialrisk factor in human cancer development. 相似文献
5.
Y Tsutsumi X Jie K Ihara A Nomura S Kanemitsu H Takada T Hara 《Diabetic medicine》2006,23(10):1145-1150
AIMS: To investigate the contribution of regulatory T cells and co-stimulatory molecules in CD4(+) T cells to the development of Type 1 diabetes (T1D). METHODS: Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE), and 12 age-matched healthy control subjects participated. We analysed the proportions of CD25(+)CD4(+) T cells and natural killer T cells (NKT cells), and the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral blood mononuclear cells and purified CD4(+) T cells. RESULTS: There were no significant differences in the proportions of CD25(+) CD4(+) T cells or NKT cells among the three groups. PD-1 expression levels of peripheral CD4(+) T cells from T1D patients were significantly lower than those from healthy control subjects (P = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and BTLA were similar in the three groups. CONCLUSIONS: Decreased expression of the PD-1 gene in CD4(+) T cells may contribute to the development and/or maintenance of autoimmune T1D. As the population studied was small and heterogeneous, further studies are required to confirm the findings. 相似文献
6.
Y. Tsutsumi T. Kihira S. Tsunoda T. Kanamori S. Nakagawa T. Mayumi 《British journal of cancer》1995,71(5):963-968
This study was conducted to increase the anti-tumour potency and reduce the toxic side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha was chemically conjugated with monomethoxy polyethylene glycol (PEG) using succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an increase in the reaction time and the initial molar ratio of PEG relative to TNF-alpha. The resulting modified TNF-alpha was separated into fractions of various molecular weights. The specific activity of separated PEG-TNF-alpha s relative to that of native TNF-alpha gradually decreased with an increase in the degree of PEG modification, but the plasma half-life was drastically increased with the increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29% and 56% of lysine residues were coupled to PEG, had anti-tumour activity approximately 4 and 100 times greater than unmodified TNF-alpha in the murine Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects, but these were not observed with the modified TNF-alpha s. Optimal PEG modification of TNF-alpha markedly increased its bioavailability and may facilitate its potential anti-tumour therapeutic use. 相似文献
7.
A 28-year-old woman with a left frontoparietal anaplastic astrocytoma was treated postoperatively with a combination of cisplatin and 1-(4-amino-2-methylpyrimidine-5-yl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). The drugs were infused via the left supraophthalmic internal carotid artery in an attempt to avoid ocular toxicity. The patient subsequently developed blindness in the left eye and a right temporal hemianopsia from marked degeneration of the left optic nerve and tract. It is apparent that the placement of a catheter into the supraophthalmic carotid artery does not exclude visual complications. 相似文献
8.
隔离饲养及给药时刻对小鼠阿米卡星药物动力学的影响 总被引:1,自引:0,他引:1
目的:研究社会环境及给药时刻对小鼠阿米卡星代谢的影响。方法:小鼠按饲养环境;隔离饲养(I)或集体饲养(A)及给药时间:日中(D)及午液(N)随机分为:I-D,I-N,A-D,A-N4组,饲养4周后于D(13:00)或N(01:00)sc阿米卡星15mg.kg^-1测定给药后血浆浓度,以开放一室模型拟合计算有关药代动力学参数,结果:A-N组阿米卡星清除较率A-D及I-N组增大,血浆半衰期变短,0-1 相似文献
9.
M. Kamberi T. Kotegawa K. Tsutsumi K. Nakamura S. Nakano 《European journal of clinical pharmacology》1998,54(8):633-637
Objective: To investigate the effect of acidification and alkalinization on the pharmacokinetics of sparfloxacin in healthy subjects.
Methods: A single 200-mg oral dose of sparfloxacin was given to nine healthy Japanese volunteers on three separate occasions under
different conditions of urinary pH. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride
and sodium bicarbonate, respectively. The concentrations of sparfloxacin and its metabolite in plasma and urine were determined
by high-performance liquid chromatography assays.
Results: The difference between treatments for Cmax, AUC∞, and CL · f−1 were found to be significant. The relative bioavailability of sparfloxacin was 84.4% and 122.3% after ammonium chloride and
sodium bicarbonate treatments, respectively. The amount of unchanged sparfloxacin in urine samples collected 0–48 h after
sparfloxacin administration represented 10.1% of the dose in the control, 14.3% of the dose in urine acidification and 8.4%
of the dose with alkalinization of urine. Renal clearance was found to depend on urinary pH. However, the plasma elimination
and the metabolism of sparfloxacin were not significantly altered by acidification or alkalinization of the urine.
Conclusion: The urinary pH dependence of the renal clearance of sparfloxacin will be of minor clinical importance with regard to the
low contribution of renal excretion to the overall elimination of sparfloxacin. On the other hand, the alteration in the environmental
pH in the gastrointestinal tract, produced by the concomitant ingestion of ammonium chloride or sodium bicarbonate, influences
the absorption and bioavailability of sparfloxacin. This effect is likely to be clinically significant.
Received: 18 March 1998 / Accepted in revised form: 1 July 1998 相似文献
10.