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1.
2.
C L DeVane 《Clinics in Laboratory Medicine》1987,7(3):551-566
Therapeutic drug monitoring of antidepressants can ensure that a reasonable amount of drug reached the circulation, can aid in dosage adjustments for treating endogenous depression, can avoid toxicity, and aid in the diagnosis of drug-induced delirium. This article reviews the justification for antidepressant monitoring, discusses sample collection procedures, and presents guidelines for the interpretation of data. 相似文献
3.
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
4.
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The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin. 相似文献
6.
Evaluation of the efficacy, safety and physiological effects of fluvoxamine in social phobia 总被引:1,自引:0,他引:1
DeVane CL Ware MR Emmanuel NP Brawman-Mintzer O Morton WA Villarreal G Lydiard RB 《International clinical psychopharmacology》1999,14(6):345-351
There is no US Food and Drug Administration (FDA) approved treatment for social phobia although data suggest efficacy for several drug classes, including beta-blockers, benzodiazepines, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). The SSRIs are particularly attractive due to their favourable tolerance and safety profile. An open label trial of fluvoxamine was conducted to evaluate its efficacy and safety in the treatment of social phobia (DSM-III-R) and to assess physiological changes that may accompany treatment. Fifteen non-depressed patients, aged 22-44 years (mean 31.6 years), entered the study. A 5-min performance task (public speaking simulation) preceded and concluded the active treatment period. Cardiovascular monitoring was performed during this time and blood sampled for plasma cortisol and steady-state plasma fluvoxamine concentration (at week 7). Ten patients (5 men and 5 women) completed an active 6 week treatment period of flexible dosing (50-150 mg/day). Five patients failed to complete the study due to drowsiness (n = 2), nausea (n = 1), or were lost to follow-up (n = 2). Analysis of clinical ratings indicated a statistically significant decrease in all scales from baseline to week 7 at the conclusion of the active treatment period. Clinical benefits were still evident at follow-up 1 week after drug discontinuation. Neither physiological effects nor plasma drug concentration correlated with clinical change. Fluvoxamine appeared to be effective and well tolerated in completers. Randomized clinical trials are needed to further demonstrate the efficacy of fluvoxamine in the treatment of social phobia. 相似文献
7.
8.
BA Evans IA Hughes CL Bevan MN Patterson JW Gregory 《Archives of disease in childhood》1997,76(6):529-531
The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone. 相似文献
9.
OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants. 相似文献
10.
Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells 总被引:2,自引:1,他引:2
p53 mutation is commonly associated with high-grade, high-stage human
urothelial carcinomas. Recent studies suggest that p53 mutation in low-
grade, low-stage bladder carcinomas may be correlated with the progression
of the disease. In the present study, we used antisense RNA methodology in
vitro to evaluate the significance of the loss of p53 function at an early
stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat
urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was
transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA
in antisense orientation. The transfection resulted in a significant
reduction in p53 mRNA expression and protein synthesis, in stimulation of
anchorage- dependent growth, and in acquisition of anchorage-independent
growth potential. Three such clones, when tested in athymic nude mice, all
formed muscle-invasive, high-grade transitional cell carcinomas at s.c.
injection sites. When cells were inoculated into an orthotopic site
(urinary bladder), one of two antisense transfectants tested formed bulky
tumors in the bladder in all seven nude mice and metastases to lungs in
three of the seven mice. Analysis of these cells revealed a decrease in the
expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene
product. Phosphorylation of Rb protein was not inhibited when the cells
were starved. No significant difference was observed in the expression of
p16 protein. In cell cycle analysis, all antisense transfectants tested
escaped from G1 arrest by starvation. Furthermore, secretion of interleukin
(IL)-6 into culture medium was increased significantly. Treatment with
anti-IL-6 antibody suppressed anchorage-dependent growth. This study
directly demonstrates that the loss of p53 function at an early stage of
urothelial carcinogenesis may result in acquisition of a malignant
phenotype by regulating IL-6 production as well as cell cycle related
genes.
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