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11.
Martin Diener Marko Bertog Michael Fromm Erwin Scharrer 《Pflügers Archiv : European journal of physiology》1996,432(2):293-300
The effect of cell swelling induced by hypotonic media was studied in segments of rat small intestine. In the Ussing chamber,
exposure to a hypotonic medium caused a decrease in short-circuit current (I
sc) and potential difference (V
ms) in the jejunum, whereas the ileum responded with an increase in I
sc and V
ms. The transition from one pattern to the other was located about in the middle of the small intestine. Tissue conductance
decreased in both segments, probably due to a reduction of paracellular shunt conductance induced by the cell swelling. Voltage
scanning experiments revealed that the observed decrease in total tissue conductance in the ileum was caused solely by a decrease
in local conductance in the villus region while the crypt conductance did not change, suggesting that the decrease in paracellular
conductance of the crypts is compensated by an increase in cellular conductance. The response in both segments was dependent
on the presence of Cl− and was blocked by the Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). It was not affected by the neurotoxin tetrodotoxin. In the
jejunum the swelling-induced decrease in I
sc was reduced in the presence of the cyclooxygenase inhibitor, indomethacin, or the lipoxygenase inhibitor, nordihydroguaiaretic
acid. In the ileum the Cl− secretion induced by hypotonicity was blocked by the K+ channel blocker quinine and was reversed into a decrease in I
sc when serosal Ca2+ was zero. We conclude that the observed volume regulatory changes are initiated in the jejunum by an eicosanoid-mediated
opening of basolateral Cl− channels and in the ileum by a Ca2+-mediated opening of K+ channels which enhances apical Cl− efflux.
Received: 27 June 1995/Received after revision: 8 December 1995/Accepted: 28 December 1995 相似文献
12.
H. Knauf E. U. Kölle E. Mutschler 《Journal of molecular medicine (Berlin, Germany)》1990,68(13):692-698
Summary The disposition of the lipid-lowering drug gemfibrozil was studied in patients with either renal (n= 8) or hepatic disease (n= 8) and compared to those of healthy volunteers (n= 6). Gemfibrozil was determined in plasma and urine by means of a HPLC method. Urine was also analyzed for gemfibrozil conjugates.Following oral administration of 900 mg gemfibrozil, maximal plasma levels of the parent drug were 46.1±15.8 g/ml, attained after 2.2±1.1 h. In chronic renal failure and in liver cirrhosis the plasma concentrations of gemfibrozil did not significantly differ from that of controls except in those patients who were comedicated with antacids. These patients had significantly lower Cmax and AUC values. The elimination half-life of the drug was 1.5 h in controls, 2.4 h in renal failure, and 2.1 h in liver disease. In healthy volunteers, only 0.02 to 0.15% of the given dose was recovered in the urine as parent gemfibrozil, while conjugates made up 7–14%. In patients with renal failure also, only traces of parent gemfibrozil could be detected, and conjugates accounted for 0.5–9.8%. In those with liver disease, however, about 0.1–0.2% were recovered in urine as parent gemfibrozil and up to 50% as conjugates. Strikingly, the amount of excreted conjugates in the urine was positively correlated to the direct bilirubin plasma concentration. It can be concluded that the elimination of gemfibrozil is not significantly influenced by renal failure. However, comedication with antacids markedly reduced plasma disposition of the drug. Patients with severe liver disease excreted more conjugated gemfibrozil via the kidney than did healthy controls. Thus, transfer across the canalicular cell membrane to the bile duct, rather than drug metabolization, is primarily disturbed in liver disease. Gemfibrozil accumulation is unlikely to occur in either kidney or liver disease.Abbreviations Clr
creatinine clearance (ml/min)
- HPLC
high pressure liquid chromatography
- Cmax
maximal plasma concentration (g/ml)
- tmax
time (h) after which Cmax is attained
- ke
elimination rate constant (h–1)
- t1/2
elimination half-life (h)
- Ae
amount of drug excreted into the urine (% of given dose)
- MRT
mean residence time (h)
- AUMC
area under the first moment curve (g h2/ml)
- AUC
area under the plasma level time curve (g·h/ml)
- ANOVA
analysis of variance
The paper is gratefully dedicated to G.W. Löhr 相似文献
13.
Marguerite Hatch Robert W. Freel N. D. Vaziri 《Pflügers Archiv : European journal of physiology》1993,423(3-4):206-212
In order to characterize oxalate handling by the P2 segment of the rabbit proximal colon, the fluxes of [14C]oxalate, 22Na+, and 36Cl– were measured in vitro using conventional short-circuiting techniques. In standard buffer the proximal colon exhibited net secretion of Na+ (–2.31±0.64 equiv cm–2 h–1), negligible net Cl– transport, and net secretion of oxalate (–12.7±1.6 pmol cm–2 h–1). Replacement of buffer Na+ or Cl– abolished net oxalate secretion, while HCO
3
–
-free media revealed a net absorption of oxalate (19.3±4.2 pmol cm–2 h–1) and stimulated NaCl absorption. Mucosal amiloride and dimethylamiloride (1 mM) significantly reduced the unidirectional fluxes of oxalate and enhanced sodium secretion by decreasing J
ms
Na
. The anion exchange inhibitor 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS; 0.1 mM, both sides) reduced the unidirectional fluxes of oxalate and chloride. Serosal epinephrine (50 M) stimulated oxalate absorption (21.3±6.3 pmol cm–2 h–1) and sodium absorption (5.71±1.20 equiv cm–2 h–1), whereas dibutyryl-cAMP enhanced oxalate secretion (–43.4±6.9 pmol cm–2 h–1) and stimulated chloride secretion (–7.27 ±0.64 equiv cm–2 h–1). These results indicate that the P2 segment of the proximal colon possesses (a) secretory as well as absorptive capacities, (b) oxalate fluxes that are mediated by pathways involving Na+, Cl–, HCO
3
–
transport and (c) a net oxalate flux that is sensitive to absorptive and secretory stimuli. 相似文献
14.
Eleven acetylsalicylic acid (ASA) formulations were administered to 26 healthy volunteers in a cross-over design. The properties of the preparations differed from conventional, effervescent, buffered to buccal. The objectives of this study were:
- 1 Consideration of the general aspects of a biopharmaceutical study: which parameter for which biopharmaceutic characteristic?
- 2 Measurement of the kinetic parameters of ASA: first-pass effect, mean residence time, mean appearance time, total body clearance, apparent volume of distribution, half-lives, etc.
- 3 Comparison of the formulations.
15.
目的:探讨氟尿嘧啶对大鼠小肠的损伤作用,方法:通过胃管连续2d给予大鼠尿嘧啶125mk/kg.d,观察给药后第1天-第7天大鼠每日饮食量的变化,给药前和给药后的第8天分别称大鼠体重,给药后第8天测定门静脉血流量及门静脉压,分析小肠形态学变化,观察小肠对色氨酸吸收能力,测定动脉血谷氨酰胺的浓度,结果:给药后第1天-第7天大鼠饮食量均明显低于正常,尤其是第2天-第4天最为严重,第8天大鼠体重下降,小肠结构有明显损伤,门静脉血流量减少,门静脉压下降,小肠对色氨酸的吸收及动脉血谷氨酸胺浓度明显下降,与对照组相比的均有显著差异,结论:氟尿嘧啶可导致大鼠小肠结构和功能的明显障碍。 相似文献
16.
Francis Kompaore Hiroshi Tsuruta 《International archives of occupational and environmental health》1993,65(Z1):S223-S225
The stratum corneum barrier function of Blacks, Caucasians and Asians were compared in vivo. A noninvasive technic, laser doppler velocimetry (LDV), was used to evaluate the cutaneous penetration of nicotinates by the determination of the lag time before vasodilatation induced by the application of those local vasodilatator drugs. The study was performed on untreated skin and after removal of the stratum corneum by 12 strips. The influence of molecular weight and solubility of different nicotinates (methyl, ethyl, hexyl and vitamin E) were also studied on Japanese skin. Vasodilatation lag times assessed by LDV, with methyl nicotinate (MN), showed that skin permeability was more important in Asians (P < 0.01)=" and=" in=" caucasians=">P < 0.05)=" than=" in=" blacks.=" moreover=" asian=" skin=" was=" significantly=" more=" sensitive=" to=" stripping=">P < 0.05)=" than=" black=" skin.=" a=" significant=" shorter=" lag=" time=" was=" obtained=" with=" small=" and=" hydrophilic=" nicotinates=" (methyl=" and=" ethyl)=">P < 0.01)=" compared=" to=" a=" lipophilic=" one=" (hexyl).=" the=" alteration=" of=" the=" stratum=" corneum=" barrier=" function=" by=" stripping=" showed=" a=" more=" important=" modification=" with=" mn=">P < 0.05)=" than=" with=" hexyl=" nicotinate.=" consequently,=" this=" noninvasive=" method=" can=" evaluate=" the=" modifications=" of=" the=" stratum=" corneum=" barrier=" function=" and=" racial=" origin=" has=" to=" be=" taken=" into=" account=" in=" the=" determination=" of=" skin="> 相似文献
17.
本文对EDTA -NaOH作为硫化氢吸收液进行探讨和研究。试验表明 :当空气中硫化氢含量为国家最高允许液度 0 .6~ 6倍时 ,吸收液采样效率为 98.2~ 10 0 % ,催化剂与显色剂混合使用 ,可降低空白值 ,提高方法灵敏度。本法准确度 ( p)为 93 .0 % ,精密度合并变异系数 (cv)为 3 .93 % ;检出限、测量限分别为 7× 10 -2 μg/5ml和1.7× 10 -1μg/5ml;规定采气量为 0 .5L时 ,则最小检出浓度为 0 .6 8mg/m3。 相似文献
18.
湖南麦饭石卫生学评价 总被引:2,自引:0,他引:2
目的 为开发利用湖南 F6、 F7 麦饭石矿物营养的有益资源。方法 毒理学试验,观察实验动物存活、生长状况;生物活性实验,证实麦饭石中微量元素对动植物的营养作用。结果 急性、80 天生长试验实际无毒,并能提高小鼠的游泳耐力,延长金鱼存活时间,花卉枯萎时间后移,伤口愈合时间缩短以及吸附水中氰化物、铅、汞、砷、镉和甲醇等有毒物质。结论 麦饭石作为矿物营养资源具有广阔的的应用前景。 相似文献
19.
Bioavailability of intranasal formulations of dihydroergotamine 总被引:1,自引:0,他引:1
van der Kuy PH Lohman JJ Hooymans PM Ter Berg JW Merkus FW 《European journal of clinical pharmacology》1999,55(9):677-680
Objective: A comparison of the pharmacokinetic properties of two novel intranasal preparations of dihydroergotamine mesilate (DHEM)
with a commercially available intranasal preparation.
Methods: Two intranasal formulations of DHEM in combination with randomly methylated β-cyclodextrin (RAMEB) were prepared. Subsequently,
in an open, randomised, crossover study in nine healthy volunteers, the following medication was administered: 2 mg DHEM/2%
RAMEB nasal spray ( =two puffs of 100 μl); 2 mg DHEM/4 mg RAMEB nasal powder; 2 mg Diergo nasal spray ( =four puffs of 125 μl);
0.5 mg DHEM i.m., and 2 mg DHEM solution p.o.
Results: No statistically significant differences were found in maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under plasma concentration–time curve (AUC0–8 h), Frel(t=8 h) and Cmax/ AUC(t=8 h) for the three intranasal preparations. The relative bioavailabilities of the DHEM/RAMEB nasal spray, the DHEM/RAMEB nasal
powder and the commercially available DHEM nasal spray were 25%, 19% and 21%, respectively, in comparison with i.m. administration.
The relative bioavailability after oral administration was 8%.
Conclusion: The pharmacokinetic properties of the novel intranasal preparations are not significantly different from the commercially
available nasal spray. Advantages of the DHEM/RAMEB nasal spray are (1) less complicated handling, (2) reduction of the number
of puffs and (3) a preference by the volunteers.
Received: 12 February 1999 / Accepted in revised form: 23 August 1999 相似文献
20.
目的 探讨磁极化生物平衡离子吸附降脂降粘疗法(也称之为洗血疗法)对老年心脑血管病危险因素的临床疗效。方法 应用磁极化生物平衡离子吸附疗法对22例老年患有心脑血管病危险因素的患者进行治疗,并对临床各项指标进行对照比较。结果 22例患者治疗前后的血流变学指标、血脂等均有明显改善。治疗前患者的TCHO(胆固醇)、TG(甘油三酯)分别为(6.21±1.14)mmol/L和(6.78±5.13)mmol/L;治疗后分别为(4.36±0.99)mmol/L和(2.41±2.10)mmol/L,P<0.05,均显著降低。治疗前患者的HCT(红细胞压积)、PFC(纤维蛋白)、NP(血浆粘度)、NR(全血粘度)、VAI(细胞聚集指数)分别为(0.441±0.042)V、(4.11±1.78)g/L、(3.86±1.98)mpa.s、(5.68±0.79)mpa.s和0.89土0.23;治疗后分别为(0.344±0,061)V、(2.21±1.12)g/L、(1.49±0.40)mpa.s、(3.21±0.56)mpa.s和0.40±0.15,治疗前后对照比较,P<0.02。结论本方法对老年人心脑血管病危险因素的治疗是有效的。 相似文献