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51.
Kroese ED; Dortant PM; van Steeg H; van Oostrom CT; van der Houven van Oordt CW; van Kranen HJ; de Vries A; Wester PW; van Kreijl CF 《Carcinogenesis》1997,18(5):975-980
E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to
their low spontaneous tumour incidence and their increased sensitivity
towards the lymphomagen ethylnitrosourea these mice may present an
interesting model for short-term carcinogenicity testing. Here, we report
on the further exploration of this transgenic mouse model with two
additional carcinogens known to have, among others, the
lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and
12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week
(by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a
dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1
mice during the observation period of 40 weeks. B[a]P also induced tumours
of the forestomach within this observation period, though at a lower
incidence and apparently equally effective in wildtype and transgenic mice.
TPA, on the other hand, was unable to induce lymphomas (or tumours in any
other organ) in either transgenic or wildtype animals within the
observation period of 44 weeks, when applied dermally at the maximum
tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular
analysis showed that B[a]P-induced lymphomas in transgenic mice were of
T-cell origin, 80% of which had elevated levels of c-myc expression. None
of the lymphomas had increased N-myc expression and mutation analysis of
the ras-gene family revealed a K-ras mutation in only one out of eight
tumours investigated. Also, none of the lymphomas showed aberrant
expression of p53 as determined by immunohistochemistry. It is concluded
that the E mu-pim-1 mouse model will not be very suitable for short-term
carcinogenicity testing in general: only genotoxic chemicals that have the
lymphohaematopoietic system as target for carcinogenesis in wild- type
mice, appear to be efficiently identified.
相似文献
52.
Philippa Howden‐Chapman Nigel Isaacs Julian Crane Ralph Chapman 《International journal of environmental health research》1996,6(3):173-185
There is a long tradition of using housing interventions to promote public health, despite causative factors being unclear. This article reviews the research evidence on the key aspects of poor housing such as inadequate maintenance, over crowding, low temperatures and dampness, that have been identified as contributing to the impact of housing on health. Possible intervening factors such as house dust mites and fungi are also reviewed. This evidence is discussed in the context of possible confounding factors such as housing location and tenure. Conclusions are drawn about the adequacy of the research evidence as a basis for changing building regulations and other policy measures as a way of improving health. 相似文献
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There is much to be gleaned from novels concerning the links between wealth and power, inequality and corruption, poverty and illness. A student of social epidemiology will profit as much from close reading of these classics as from consulting textbooks on social stratification. 相似文献
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58.
Sharma VK Peyton B Spears T Raufman JP Howden CW 《Alimentary pharmacology & therapeutics》2000,14(7):887-892
BACKGROUND: Omeprazole and lansoprazole can be given in sodium bicarbonate as, respectively, simplified omeprazole suspension and simplified lansoprazole suspension. We previously found the antisecretory effect of omeprazole 20 mg given as simplified omeprazole suspension to be lower than with intact capsules. However, lansoprazole 30 mg as simplified lansoprazole suspension produced an effect similar to that seen with intact capsules. AIM: To evaluate the absorption of both drugs when given orally as capsules or as suspensions in sodium bicarbonate. METHODS: In random order, we gave 5-day courses of omeprazole 20 mg and lansoprazole 30 mg as capsules and as suspensions in sodium bicarbonate to 12 healthy women. Serial blood samples were taken on days 1 and 5 of each course for pharmacokinetic measurements. RESULTS: There was impairment of omeprazole absorption when given as simplified omeprazole suspension. Maximum plasma concentration and area under the concentration/time curve were lower with simplified omeprazole suspension than with omeprazole capsules (P=0.034 and 0.013, respectively, on day 5). No differences were found in lansoprazole absorption when simplified lansoprazole suspension was compared with its standard capsule formulation. Relative bioavailability of omeprazole from simplified omeprazole suspension compared to the capsule was 58.4% on day 5. The corresponding value for lansoprazole was 84.7%. CONCLUSIONS: Simplified omeprazole suspension 20 mg does not supply adequate omeprazole for systemic absorption. Lansoprazole absorption from simplified lansoprazole suspension is maintained. 相似文献
59.
N.E. Holmes J.D. Turnidge W.J. Munckhof J.O. Robinson T.M. Korman M.V.N. O'Sullivan T.L. Anderson S.A. Roberts S.J.C. Warren W. Gao P.D.R. Johnson B.P. Howden 《Clinical microbiology and infection》2013,19(12):1163-1168
We reported an association between elevated vancomycin MIC and 30-day mortality in patients with Staphylococcus aureus bacteraemia (SAB), including patients with methicillin-susceptible S. aureus (MSSA) treated with flucloxacillin. A detailed analysis of comorbidities and disease severity scores in the same cohort of patients was performed to ascertain if unknown clinical parameters may have influenced these results. The association between elevated vancomycin MIC and 30-day mortality in SAB remained significant (p 0.001) on multivariable logistic regression analysis even when accounting for clinical factors. In addition, the association persisted when restricting analysis to patients with MSSA bacteraemia treated with flucloxacillin. This suggests that elevated vancomycin MIC is associated with but not causally linked to an organism factor that is responsible for increased mortality. 相似文献
60.
The toxin from Hapalochlaena maculosa (the blue-ringed octopus) has been isolated in a chromatographically pure state. The toxin (maculotoxin) is a stable, highly polar compound, having a relatively low molecular weight. Maculotoxin behaves as a cation under certain conditions and was shown to be chemically similar to, but distinct from, tetrodotoxin. 相似文献