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91.
van Heeswijk RP Veldkamp AI Mulder JW Meenhorst PL Beijnen JH Lange JM Hoetelmans RM 《Therapeutic drug monitoring》2001,23(3):255-258
The objective of this study was to evaluate the applicability of saliva as an alternative body fluid for therapeutic drug monitoring of nevirapine. The pharmacokinetics of nevirapine in plasma and saliva during a dosing interval was assessed in HIV-1-infected patients taking nevirapine (200 mg twice daily) to explore the relation between the concentration of nevirapine in plasma and saliva. To validate the anticipated relationship prospectively, single, paired plasma and saliva samples were obtained from nevirapine-treated HIV-1-infected outpatients. The plasma nevirapine concentration was strongly correlated with the salivary concentration. The mean saliva/plasma concentration ratio was 0.51 and was independent of the time after ingestion. Salivary nevirapine concentrations were used to estimate the corresponding plasma concentrations for 31 outpatients. Compared with the true plasma concentrations, the estimated concentrations were biased by -4.2%, with a precision of 13.3%. These data show a strong correlation between the salivary and plasma concentrations of nevirapine at a dosage of 200 mg twice daily. This relation has been validated prospectively, and the prediction of plasma concentrations was accurate and precise. Therefore, the authors conclude that saliva can be a useful body fluid for therapeutic drug monitoring of nevirapine. 相似文献
92.
Excel97在药物分析中的应用 总被引:1,自引:0,他引:1
目的:在药物分析中,电子表格软件MicrosoftExce197for Windows。方法:利用Excel的数据处理功能,进行药物的图表绘制、数据计算和统计处理,回归分析,特别是计算分析,并可建立分析数据库。结果和结论:Excel操作简单,功能强大,数据分析工作直观。 相似文献
93.
目的:比较国产辛伐他汀与进口辛伐他汀治疗原发性高胆固醇血症的疗效及安全性。方法:采用开放区组随机对照、多中心的临床设计。150例高胆 固醇血症病人分为验证组(50例)、对照组(48例)和开放组(52例),剂量均为每晚顿服10mg,服药8周。结果:验证组与对照组服药前后比较,血清总胆 固醇(TC)分别降低26.36%和28.3%,低密度脂蛋白胆固醇(LDL-C)分别降低33.17%和35.51%;验 相似文献
94.
Diet and cancer prevention: the fiber first diet 总被引:3,自引:0,他引:3
Diet can play a major role in cancer prevention. The international
differences in cancer incidence are largely accounted for by lifestyle
practices that include nutrition, exercise, and alcohol and tobacco use.
About 50% of cancer incidence and 35% of cancer mortality in the U.S.,
represented by cancers of the breast, prostate, pancreas, ovary,
endometrium, and colon, are associated with Western dietary habits. Cancer
of the stomach, currently a major disease in the Far East, relates to
distinct, specific nutritional elements such as excessive salt intake. For
these cancers, information is available on possible initiating genotoxic
factors, promoting elements, and prophylactic agents. In general, the
typical diet in the United States contains low levels of the potent
carcinogenic agents, heterocyclic amines, formed during the cooking of
meats. It provides only about half the potent appropriate fiber intake and
is high in calories. About twice as many calories as would be desirable
come from fat, certain kinds of which enhance the development of cancers.
Other foods with functional properties, such as soy products and tea, can
be beneficial. To achieve reduction in risk of certain cancers, diet must
be optimized, primarily to reduce caloric intake and the fat component. The
latter should be 20% or less of total caloric intake and fiber should be
increased to 25- 35 g per day for adults. One approach to achieving these
goals is the Fiber First Diet, a diet designed around adequate fiber intake
from grains, especially cereals, vegetables, legumes, and fruits, which
thereby reduces both calorie and fat intake. Such dietary improvements will
not only reduce cancer and other chronic disease risks, but will contribute
to a healthy life to an advanced age. A corollary benefit is a lower cost
of medical care.
相似文献
95.
van Gijn R ten Bokkel Huinink WW Rodenhuis S Vermorken JB van Tellingen O Rosing H van Warmerdam LJ Beijnen JH 《Anti-cancer drugs》1999,10(1):17-23
Intoplicine, an antitumor drug which interacts with both topoisomerase enzymes I and II, has demonstrated a broad spectrum of activity in preclinical studies. This indicates further clinical evaluation. In the present phase I study, with the primary objective to determine the maximum tolerated dose, intoplicine was administered by a 24 h continuous infusion every 21 days to 32 patients with solid malignant tumors. The patients received 12-640 mg/m2 by a central venous catheter. Liver toxicity was dose limiting. One patient died in a hepatic coma after the first course (dose 640 mg/m2), which was associated with intoplicine treatment. Other side effects were sporadic and mild. Myelotoxicity was virtually absent. Twenty-two patients had stable disease for four to six courses of treatment. The plasma concentration-time curves were compatible with standard linear pharmacokinetic models, with a protracted terminal half-life (mean 115 h). Although one sudden death occurred probably due to intoplicine toxicity, we nevertheless feel that research with intoplicine should continue, mainly because of its preclinical activity and its unique mechanism of action. The recommended dose for phase II studies with intoplicine administered as a 24 h infusion is 384 mg/m2. Liver toxicity, also seen in studies employing other dosages and infusion durations, should be investigated extensively in further clinical studies. 相似文献
96.
Kuin A Aalders M Lamfers M van Zuidam DJ Essers M Beijnen JH Smets LA 《British journal of cancer》1999,79(5-6):793-801
Tumour-selective acidification is of potential interest for enhanced therapeutic gain of pH sensitive drugs. In this study, we investigated the feasibility of a tumour-selective reduction of the extracellular and intracellular pH and their effect on the tumour response of selected anti-cancer drugs. In an in vitro L1210 leukaemic cell model, we confirmed enhanced cytotoxicity of chlorambucil at low extracellular pH conditions. In contrast, the alkylating drugs melphalan and cisplatin, and bioreductive agents mitomycin C and its derivative EO9, required low intracellular pH conditions for enhanced activation. Furthermore, a strong and pH-independent synergism was observed between the pH-equilibrating drug nigericin and melphalan, of which the mechanism is unclear. In radiation-induced fibrosarcoma (RIF-1) tumour-bearing mice, the extracellular pH was reduced by the mitochondrial inhibitor m-iodobenzylguanidine (MIBG) or its analogue benzylguanidine (BG) plus glucose. To simultaneously reduce the intracellular pH, MIBG plus glucose were combined with the ionophore nigericin or the Na+/H+ exchanger inhibitor amiloride and the Na+-dependent HCO3-/Cl- exchanger inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS). Biochemical studies confirmed an effective reduction of the extracellular pH to approximately 6.2, and anti-tumour responses to the interventions indicated a simultaneous reduction of the intracellular pH below 6.6 for at least 3 h. Combined reduction of extra- and intracellular tumour pH with melphalan increased the tumour regrowth time to 200% of the pretreatment volume from 5.7 +/- 0.6 days for melphalan alone to 8.1 +/- 0.7 days with pH manipulation (P < 0.05). Mitomycin C related tumour growth delay was enhanced by the combined interventions from 3.8 +/- 0.5 to 5.2 +/- 0.5 days (P < 0.05), but only in tumours of relatively large sizes. The interventions were non-toxic alone or in combination with the anti-cancer drugs and did not affect melphalan biodistribution. In conclusion, we have developed non-toxic interventions for sustained and selective reduction of extra- and intracellular tumour pH which potentiated the tumour responses to selected anti-cancer drugs. 相似文献
97.
Pharmaceutical development of a parenteral lyophilized formulation of the novel antitumor agent aplidine 总被引:2,自引:0,他引:2
Nuijen B Bouma M Henrar RE Floriano P Jimeno JM Talsma H Kettenes-van den Bosch JJ Heck AJ Bult A Beijnen JH 《PDA journal of pharmaceutical science and technology / PDA》2000,54(3):193-208
Aplidine is a naturally occurring cyclic depsipeptide isolated from the Mediterranean tunicate Aplidium albicans. Aplidine displays promising in vitro and in vivo antitumor activities against various solid human tumor xenografts and is therefore developed now for clinical testing. The aim of this study was to develop a stable parenteral pharmaceutical dosage form for clinical Phase I testing. Aplidine raw material was characterized by using several chromatographic and spectrometric techniques. These experiments showed that aplidine exists as two isomers. A stability-indicating HPLC assay was developed. Solubility testing showed that aplidine exhibits very poor aqueous solubility. Because solubilized aplidine showed substantial degradation under heat and light stress testing conditions, it was decided to develop a lyophilized dosage form. Freeze-drying was carried out with a 500 micrograms/mL solution of aplidine in 40% (v/v) tert-butanol in Water for Injection (WfI) containing 25 mg/mL D-mannitol as a bulking agent. Differential scanning calorimetry was applied to determine the optimal freeze-drying cycle parameters. The prototype, containing 500 micrograms aplidine and 25 mg D-mannitol per vial, was found to be the optimal formulation in terms of solubility, length of lyophilization cycle, and dosage requirements in the forthcoming Phase I clinical studies. Quality control of the freeze-dried formulation demonstrates that the manufacturing process does not affect the integrity of aplidine. The optimal reconstitution solution was found to be 15/15/70% (v/v/v) Cremophor EL/ethanol/WfI (CEW). Both reconstituted product and dilutions of the reconstituted product with normal saline (up to 1:100 v/v) appeared to be stable for at least 24 hours after preparation. Shelf-life data, available thus far, show that the lyophilized formulation is stable for at least 1 year when stored at +2-8 degrees C in the dark. 相似文献
98.
99.
100.
R E Brolin MD JH Gorman MD RC Gorman MD AJ Petschenik M D LJ Bradley MS RD HA Kenler PhD RP Cody Pb D 《Journal of gastrointestinal surgery》1998,2(5):436-442
Although iron, vltamm B12, and folate deficiency have been well documented after gastric bypass operations performed for morbid obesity, there is surprisingly
little information on either the natural course or the treatment of these deficiencies in Roux-en-Y gastric bypass (RYGB)
patients Durmg a l0-year period, a complete blood count and serum levels of iron, total iron-binding capacity, vltamin B12, and folate were obtained in 348 patients preoperatively and postoperatively at 6-month intervals for the first 2 years,
then annually thereafter The principal objectives of this study were to determine how readily patients who developed metabolic
deficiencies after Roux-en-Y gastric bypass responded to postoperative supplements of the deficient micronutrient and to learn
whether the risk of developmg these deficiencies decreases over time Hemoglobin and hematocrit levels were slgnificantly decreased
at all postoperative intervals in comparison to preoperative values Moreover, at each successive interval through 5 years,
hemoglobin and hematocrit were decreased signifiantly compared to the preceding interval Folate levels were significantly
increased compared to preoperative levels at all time intervals Iron and vltamin B12 levels were lower than preoperative measurements and remained relatively stable postoperatively Half of the low hemoglobin
levels were not associated with iron deficiency Taking multivltamin supplements resulted in a lower incidence of folate deficiency
but did not prevent iron or vitamin B12 deficiency Oral supplementation of iron and vitamin B12 corrected defiaencies in 43% and 81% of cases, respectively Folate deficiency was almost always corrected with multivitamins
alone No patient had symptoms that could be attributed to either vitamin B12 or folate deficiency Conversely, many patients had symptoms of iron deficiency and anenua Lack of symptoms of vitamin B12 and folate deficiency suggests that these deficiencies are not clinically important after RYGB Conversely, iron deficiency
and anemia are potentially serious problems after RYGB, particularly in younger women Hence we recommend prophylactic oral
iron supplements to premenopausal women who undergo RYGB 相似文献