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991.
992.
B Baroli G Delogu A M Fadda G Podda C Sinico 《International journal of pharmaceutics》1999,183(2):101-107
Hexakis[butoxytris(ethoxy)]cyclophosphazene (3a), hexakis[dodecyloxytetrakis (ethoxy)]cyclophosphazene (3b) and hexakis[hexadecyloxyeicosanekis(ethoxy)]cyclophosphazene+ ++ (3c) were synthesised and their ability to form niosomes was studied. All synthesised compounds in the presence of cholesterol were shown to form vesicles, which aggregated strongly. To prevent aggregation, dicetylphosphate was used. The capacity of the sonicated and unsonicated niosomes to encapsulate hydrophile and lipophile molecules was also studied using carboxyfluorescein and diphenylhexatriene. 相似文献
993.
Zakharova VM Serpi M Krylov IS Peterson LW Breitenbach JM Borysko KZ Drach JC Collins M Hilfinger JM Kashemirov BA McKenna CE 《Journal of medicinal chemistry》2011,54(16):5680-5693
Eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine P-O esters of cyclic cidofovir ((S)-cHPMPC, 4) and its cyclic adenine analogue ((S)-cHPMPA, 3) were synthesized and evaluated as prodrugs. In vitro IC(50) values for the prodrugs (<0.1-50 μM) vs vaccinia, cowpox, human cytomegalovirus, and herpes simplex type 1 virus were compared to those for the parent drugs ((S)-HPMPC, 2; (S)-HPMPA, 1; IC(50) 0.3-35 μM); there was no cytoxicity with KB or HFF cells at ≤100 μM. The prodrugs exhibited a wide range of half-lives in rat intestinal homogenate at pH 6.5 (<30-1732 min) with differences of 3-10× between phostonate diastereomers. The tyrosine alkylamide derivatives of 3 and 4 were the most stable. (l)-Tyr-NH-i-Bu cHPMPA (11) was converted in rat or mouse plasma solely to two active metabolites and had significantly enhanced oral bioavailability vs parent drug 1 in a mouse model (39% vs <5%). 相似文献
994.
Errasti-Murugarren E Díaz P Godoy V Riquelme G Pastor-Anglada M 《Molecular pharmacology》2011,80(5):809-817
The plasma membrane distribution and related biological activity of nucleoside transporter proteins (NTs) were investigated in human syncytiotrophoblast from term placenta using a variety of approaches, including nucleoside uptake measurements into vesicles from selected plasma membrane domains, NT immunohistochemistry, and subcellular localization (basal, heavy, and light apical membranes as well as raft-enriched membranes from the apical domain). In contrast with other epithelia, in this epithelium, we have identified the high-affinity pyrimidine-preferring human concentrative nucleoside transporter (hCNT) 1 as the only hCNT-type protein expressed at both the basal and apical membranes. hCNT1 localization in lipid rafts is also dependent on its subcellular localization in the apical plasma membrane, suggesting a complex cellular and regional expression. Overall, this result favors the view that the placenta is a pyrimidine-preferring nucleoside sink from both maternal and fetal sides, and hCNT1 plays a major role in promoting pyrimidine salvage and placental growth. This finding may be of pharmacological relevance, because hCNT1 is known to interact with anticancer nucleoside-derived drugs and other molecules, such as nicotine and caffeine, for which a great variety of harmful effects on placental and fetal development, including intrauterine growth retardation, have been reported. 相似文献
995.
Medana C Calza P Giancotti V Dal Bello F Pasello E Montana M Baiocchi C 《Drug testing and analysis》2011,3(10):724-734
Two horses were treated with sildenafil, and its metabolic products were sought in both urine and plasma samples. Prior to this, a simulative laboratory study had been done using a photocatalytic process, to identify all possible main and secondary transformation products, in a clean matrix; these were then sought in the biological samples. The transformation of sildenafil and the formation of intermediate products were evaluated adopting titanium dioxide as photocatalyst. Several products were formed and characterized using the HPLC/HRMS(n) technique. The main intermediates identified in these experimental conditions were the same as the major sildenafil metabolites found in in vivo studies on rats and horses. Concerning horse metabolism, sildenafil and the demethylated product (UK 103,320) were quantified in blood samples. Sildenafil propyloxide, de-ethyl, and demethyl sildenafil, were the main metabolites quantified in urine. Some more oxidized species, already formed in the photocatalytic process, were also found in urine and plasma samples of treated animals. Their formation involved hydroxylation on the aromatic ring, combined oxidation and dihydroxylation, N-demethylation on the pyrazole ring, and hydroxylation. These new findings could be of interest in further metabolism studies. 相似文献
996.
Bahamondes L Bahamondes MV Fernandes AM Monteiro I 《Expert opinion on emerging drugs》2011,16(2):373-387
INTRODUCTION: Fifty years after the first contraceptive, the market remains restricted regarding composition, cost and routes of administration, and satisfying the needs of millions of women with different requirements according to their stage in life. AREAS COVERED: Women need contraception for almost 30 years of their life. Currently available contraceptives are highly effective with few side effects. This review provides information on emerging female contraceptives including some registered and others at different stages of development. Research efforts aim to reduce costs, improve acceptability and refine 'forgettable' reversible methods. Although developing and testing a new method is laborious and expensive, many new contraceptives are currently under development including different routes of administration. EXPERT OPINION: New methods should be affordable, simple to use and suitable for many women. Much work remains to be done and new methods that act on the fusion process between both gametes are desirable without affecting the hormonal milieu. 相似文献
997.
Pala V Sieri S Berrino F Vineis P Sacerdote C Palli D Masala G Panico S Mattiello A Tumino R Giurdanella MC Agnoli C Grioni S Krogh V 《International journal of cancer. Journal international du cancer》2011,129(11):2712-2719
Fermented dairy products like yogurt have been suggested to protect against colorectal cancer (CRC). We conducted a prospective study on 45,241 (14,178 men; 31,063 women) volunteers of the EPIC-Italy cohort who completed a dietary questionnaire including specific questions on yogurt intake. During 12 years of follow-up, 289 volunteers were diagnosed with CRC. Hazard ratios (HRs) for the disease and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models, stratified by dietary questionnaire and adjusted for energy intake and other potential confounders. Yogurt intake was inversely associated with CRC risk. For the energy-adjusted model, HR for CRC in the highest versus lowest tertile of yogurt intake was 0.62 (95% CI, 0.46-0.83). In the full model adjusted for energy, simple sugar, calcium, fiber, animal fat, alcohol and red meat intake, as well as body mass index, smoking, education and physical activity, HR was 0.65 (95% CI, 0.48-0.89) in the highest versus lowest tertile. The protective effect of yogurt was evident in the entire cohort, but was stronger in men, although there was no interaction of sex with the yogurt-CRC association (p(interaction) 0.20, fully adjusted model). In our prospective study, high yogurt intake was significantly associated with decreased CRC risk, suggesting that yogurt should be part of a diet to prevent the disease. Investigation of larger cohorts is necessary to reveal any residual confounding of the association of yogurt intake with CRC risk. 相似文献
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