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91.
Percutaneous absorption of 2,6-di-tert-butyl-4-nitrophenol (DBNP) in isolated perfused porcine skin.
Alfred O Inman Kenneth R Still Warren W Jederberg Robert L Carpenter Jim E Riviere James D Brooks Nancy A Monteiro-Riviere 《Toxicology in vitro》2003,17(3):289-292
DBNP (2,6-di-tert-butyl-4-nitrophenol) has been reported as a potential contaminant in submarines. This yellow substance forms when lubrication oil mist containing the antioxidant additive 2,6-di-tert-butylphenol passes through an electrostatic precipitator and is nitrated. Percutaneous absorption of 14C-DBNP was assessed in the isolated perfused porcine skin flap (IPPSF). Four treatments were studied (n=4 flaps/treatment): 40.0 microgram/cm(2) in 100% ethanol; 40.0 microgram/cm(2) in 85% ethanol/15% H(2)O; 4.0 microgram/cm(2) in 100% ethanol; and 4.0 microgram/cm(2) in 85% ethanol/15% water. DBNP absorption was minimal across all treatment groups, with the highest absorption detected being only 1.08% applied dose in an aqueous ethanol group. The highest mass of 14C-DBNP absorbed was only 0.5 microgram. The majority of the applied dose remained on the surface of the skin. This suggests that there is minimal dermal exposure of DBNP when exposed topically to skin. 相似文献
92.
Siberian ginseng (Eleutheroccus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers. 总被引:3,自引:0,他引:3
Jennifer L Donovan C Lindsay DeVane Kenneth D Chavin Robin M Taylor John S Markowitz 《Drug metabolism and disposition》2003,31(5):519-522
Siberian ginseng ([SG]; Eleutherococcus senticosus) is a commonly used herbal preparation. The objective of this study was to assess in normal volunteers (n = 12) the influence of a standardized SG extract on the activity of cytochrome P450 CYP2D6 and 3A4. Probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again following treatment with SG (1 x 485 mg twice daily) for 14 days. Urinary concentrations of dextromethorphan and dextorphan were quantified, and dextromethorphan metabolic ratios (DMRs) were determined at baseline and after SG treatment. Likewise, plasma samples were collected (0-60 h) for alprazolam pharmacokinetics at baseline and after SG treatment to assess effects on CYP3A4 activity. Validated high performance liquid chromatography methods were used to quantify all compounds and relevant metabolites. There were no statistically significant differences between pre- and post-SG treatment DMRs indicating a lack of effect on CYP2D6 (P > 0.05). For alprazolam there also were no significant differences in the pharmacokinetic parameters determined by noncompartmental modeling (C(max), T(max), area under the curve, half-life of elimination) indicating that SG does not significantly induce or inhibit CYP3A4 (P > 0.05). Our results indicate that standardized extracts of SG at generally recommended doses for over-the-counter use are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination. 相似文献
93.
Liselott Muhlen-Schulte Kenneth Wade 《Australian and New Zealand journal of public health》1988,12(1):69-81
This paper is a report of a study of obstetric intervention in childbirth and its effects on neonatal behaviour. Interventions included anaesthesia, augmentation, induction and caesarean section and their relationships to behavioural responsiveness of the babies over the neonatal period were examined. Among the 120 mothers, the study found considerable rates of intervention into childbirth. Babies were assessed on three occasions using the Brazelton Neonatal Behavioral Assessment Scale (NBAS). Data from one hundred and nine babies were analysed. Babies whose mothers had epidural anaesthesia were less likely to achieve optimal Motoric subscale scores than babies whose mothers did not. A lower percentage of caesarean birth babies than vaginal birth babies achieved optimal scores on the State Control, Interaction and Motoric subscales of the NBAS. It is recommended that every effort be made to reduce the high caesarean section rate, the rates of other interventions, such as induction and the levels of use of epidural anaesthesia and episiotomy. A preferred way to do this would be to make a more natural birth available to all but the truly high-risk population. 相似文献
94.
Kenneth W. Locke Robert W. Dunn John W. Hubbard Cheri L. Vanselous Michael Cornfeldt Stuart Fielding Joseph T. Strupczewski 《Drug development research》1990,19(3):239-256
HP 818 (1-benzoyl-6-fluoro-3-(1-methyl-4-piperidinyl)-1H-indazole) exhibits the profile of a potent nonnarcotic analgesic with neuroleptic properties. HP 818 blocks the effects of chemical (phenylquinone), pressure (tail clip), and radiant heat (tail flick) painful stimuli in mice (ED50 values of 0.3, 1.2, and 4.1 mg/kg s.c., respectively). This compound displays antinociceptive activity by the subcutaneous, oral, and intravenous routes of administration. It is also effective in the shock titration assay in squirrel monkeys and in a model of surgically induced pain. The rank order of potency of HP 818 and several other standard compounds in these tests for analgesia was Innovar > fentanyl > HP 818 > codeine > droperidol. In addition to its antinociceptive effects, HP 818 possesses neuroleptic properties. It is active in the climbing mouse, pole climb avoidance, and intracranial self-stimulation assays (ED50 values of 1.8, 1.7, and 2.5 mg/kg i.p., respectively). Moreover, HP 818 inhibits amphetamine- and apomorphine-induced stereotypy, indicative of D2-dopaminergic blocking properties. HP 818, unlike typical neuroleptic agents, does not induce supersensitivity to the effects of apomorphine when administered chronically in mice. In contrast to the clinical standard neuroleptanalgesic Innovar, HP 818 (1.0–3.0 mg/kg i.v.) produces no significant cardiovascular or respiratory changes in the anesthetized dog. Thus, HP 818 is potentially an effective presurgical medication due to its nonnarcotic analgesic activity and sedative neuroleptic effects, along with its lack of limiting cardiorespiratory side effects. 相似文献
95.
96.
French Donna L. Häglund Bert O. Himmelstein Kenneth J. Mauger John W. 《Pharmaceutical research》1995,12(10):1513-1520
Purpose. The objective of this study is to correlate drug release mechanism with measured drug concentration profiles in gel layers of Carbopol® matrices containing mesalamine or benzoic acid.
Methods. Release rate experiments with Carbopol® matrices were performed using a rotating disk apparatus. Matrices were frozen and the gel layer in the matrices was sliced using a microtome in a cryostat. Drug concentration profiles were determined by direct measurement of the concentration of the drug in the gel slices. The pH of the slices was measured using microelectrodes, and water content was measured by Karl Fisher titration.
Results. The concentration gradient in mesalamine matrices decreased over time and correlated with square root of time release rate kinetics. The concentration profiles of benzoic acid were unchanged over time and correlated with zero order release rate kinetics. Carbopol gel layers were highly hydrated (93–95% water). Gel layers in matrices with mesalamine had a more alkaline microenvironmental pH. This higher pH resulted in increased growth of the thickness of the gel layer and a reduction drug diffusivity in comparison to benzoic acid matrices.
Conclusions. The release rate kinetics of mesalamine and benzoic acid correlated to the measured concentration profiles. The shape of the concentration profiles is determined by the rate of growth of the Carbopol® gel layer and drug diffusivity. 相似文献
97.
Gregory P Crucian Anna M Barrett David W Burks Alonso R Riestra Heidi L Roth Ronald L Schwartz William J Triggs Dawn Bowers William Friedman Melvin Greer Kenneth M Heilman 《Journal of the International Neuropsychological Society》2003,9(7):1078-1087
Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated. 相似文献
98.
Kenneth C. Chu Barry A. Miller Eric J. Feuer Benjamin F. Hankey 《Journal of clinical epidemiology》1994,47(12):1451-1461
U.S. cancer mortality data derived from information recorded on death certificates are frequently relied upon as an indicator of progress against cancer. A limitation of this measure is the lack of information pertaining to the onset of disease, such as year-of-diagnosis, age-at-diagnosis, stage of disease at diagnosis and histology of lesions. However, population-based cancer registries collect these types of data and allow the calculation of an incidence-file based mortality rate. This incidence-based mortality rate allows a partitioning of mortality by variables associated with the cancer onset. Breast cancer incidence-based mortality measures are created and compared to mortality rates based on death certificates over a comparable time period. Novel mortality measures, such as mortality rates by stage-at-diagnosis, age-at-diagnosis and year-of-diagnosis, are used to illustrate the value of this approach. 相似文献
99.
100.