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排序方式: 共有291条查询结果,搜索用时 11 毫秒
51.
Abbas R Hug BA Leister C Sonnichsen D 《International journal of cancer. Journal international du cancer》2012,131(3):E304-E311
Effects of therapeutic and supratherapeutic concentrations of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, on the corrected QT interval (QTc) in 60 healthy adults were assessed, according to ICH-E14 guidelines, in this 2-part, randomized, single-dose, double-blind, crossover, placebo- and open-label moxifloxacin-controlled study. Subjects received placebo, moxifloxacin and bosutinib 500 mg with food (therapeutic) in Part 1. In Part 2, subjects received placebo and bosutinib 500 mg plus ketoconazole (supratherapeutic). ANOVA compared baseline-adjusted QTc for bosutinib with placebo; and bosutinib plus ketoconazole with placebo plus ketoconazole. Primary endpoint was population-specific QT correction (QTcN). Secondary endpoints were Bazett QT correction (QTcB), Fridericia's formula QT correction (QTcF) and individual QT correction (QTcI). Upper bounds for 90% confidence intervals were <10 msec for the mean change in QTcN from placebo at all postdose time points, suggesting that mean therapeutic exposures (C(max) , 114 ng/mL; AUC, 2,330 ng · h/mL) and mean supratherapeutic exposures (C(max) , 326 ng/mL; AUC, 15,200 ng · h/mL) were not associated with QTc changes. Similar results were obtained for QTcB, QTcF and QTcI. No clinically relevant pharmacokinetic/pharmacodynamic relationship was observed between bosutinib concentrations and QTc. No subjects had QTcB, QTcF, QTcI or QTcN >450 msec or change from baseline >30 msec. In summary, therapeutic and supratherapeutic bosutinib exposures are not associated with QTc prolongation in healthy adults. 相似文献
52.
Purpose
Neratinib, a potent, low-molecular-weight, orally administered, irreversible, pan-ErbB receptor tyrosine kinase inhibitor has antitumor activity in ErbB2 + breast cancer. The objective of this study was to characterize the onset, severity, and duration of diarrhea after administration of neratinib 240 mg once daily (QD) and 120 mg twice daily (BID) for ≤14 days in healthy subjects.Methods
A randomized, double-blind, parallel-group, inpatient study was conducted in 50 subjects given oral neratinib either 240 mg QD or 120 mg BID with food for ≤14 days. The primary endpoint was the proportion of subjects with diarrhea of at least moderate severity (grade 2; 5–7 loose stools/day). In subjects with grade 2 diarrhea, fecal analytes were determined. Pharmacokinetic profiles were characterized for neratinib on Days 1 and 7.Results
No severe (grade 3) diarrhea was reported. By Day 4, all subjects had grade 1 diarrhea. Grade 2 diarrhea occurred in 11/22 evaluable subjects (50 % [90 % confidence interval (CI): 28–72 %]) in the QD group and 17/23 evaluable subjects (74 % [90 % CI: 52–90 %]) in the BID group (P = 0.130). In fecal analyses, 18 % tested positive for hemoglobin and 46 % revealed fecal lactoferrin. Specimen pH was neutral to slightly alkaline. In pharmacokinetic analyses, Day 1 peak plasma concentration and Day 7 steady-state exposure were higher with the QD regimen than the BID regimen. In an exploratory analysis, ABCG2 genotype showed no correlation with severity or onset of diarrhea.Conclusions
Incidences and onsets of at least grade 1 and at least grade 2 diarrhea were not improved on BID dosing compared with QD dosing. 相似文献53.
54.
Guenter P Hicks RW Simmons D Crowley J Joseph S Croteau R Gosnell C Pratt NG Vanderveen TW 《Joint Commission journal on quality and patient safety / Joint Commission Resources》2008,34(5):285-92, 245
A consortium of organization identified solutions to the problem of enteral feeding misconnections in three areas: (1) education, awareness, and human factors; (2) purchasing strategies; and (3) design changes. 相似文献
55.
Microglial cells are central to brain immunity and intervene in many human neurological diseases. The aim of this study was to develop a convenient cellular model for human microglial cells, suitable for HIV studies. Microglia derive from the hematogenous myelomonocytic lineage, possibly as a distinct subpopulation but in any case able to invade the CNS, proliferate, and differentiate into ameboid and then ramified microglia in the adult life. We thus attempted to derive microglia-like cells from human monocytes. When cultured with astrocyte-conditioned medium (ACM), monocytes acquired a ramified morphology, typical of microglia. They overexpressed substance P and the calcium binding protein Iba-1 and dimly expressed class II MHC, three characteristics of microglial cells. Moreover, they also expressed a potassium inward rectifier current, another microglia-specific feature. These monocyte-derived microglia-like cells (MDMi) were CD4(+)/CD14(+), evocative of an activated microglia phenotype. When treated with lipopolysaccharide (LPS), MDMi lost their overexpression of substance P, which returned to untreated monocyte-derived macrophage (MDM) level. Compared with MDM, MDMi expressed higher CD4 but lower CCR5 levels; they could be infected by HIV-1(BaL), but produced less virus progeny than MDM did. This model of human microglia may be an interesting alternative to primary microglia for large scale in vitro HIV studies and may help to better understand HIV-associated microgliosis and chronic inflammation in the brain. 相似文献
56.
Richat Abbas Stephan Chalon Cathie Leister Myriam El Gaaloul Daryl Sonnichsen 《Cancer chemotherapy and pharmacology》2013,71(1):123-132
Purpose
Bosutinib, a dual Src/Abl kinase inhibitor in development for treatment of chronic myeloid leukemia, is primarily metabolized by the CYP3A4 hepatic enzyme. This study evaluated the pharmacokinetics and safety of bosutinib in patients with chronic hepatic impairment and matched healthy subjects.Methods
Hepatically impaired patients were aged 18–65 years and of Child-Pugh classes A, B, or C; healthy subjects were matched by age, sex, body mass index, and smoking habits. A single oral dose of bosutinib 200 mg was administered on day 1 within 5 min after completion of breakfast.Results
Compared with healthy subjects (n = 9), maximal plasma concentration (C max) and area under the curve increased 2.42-fold and 2.25-fold in Child-Pugh A (n = 6), 1.99-fold and 2.0-fold in Child-Pugh B (n = 6), and 1.52-fold and 1.91-fold in Child-Pugh C patients (n = 6). Time to C max decreased from 4 h in healthy subjects to 2.5, 2.0, and 1.5 h in Child-Pugh A, B, and C patients, respectively; the elimination half-life increased from 55 h in healthy subjects to 86, 113, and 111 h in Child-Pugh A, B, and C patients. Bosutinib oral clearance was lower in hepatically impaired patients compared with healthy subjects. Frequently reported adverse events included prolonged QTc interval (37.0 %, n = 10), nausea (11.1 %, n = 3), and vomiting (7.4 %, n = 2).Conclusions
A single oral dose of bosutinib 200 mg showed acceptable tolerability in healthy subjects and in patients with mild, moderate, or severe chronic hepatic impairment. 相似文献57.
Wijesinghe Printha Nunez Desmond A. Garnis Cathie 《Journal of the Association for Research in Otolaryngology》2022,23(4):467-489
Journal of the Association for Research in Otolaryngology - MicroRNAs (miRNAs) regulate gene expressions and control a wide variety of cellular functions. House Ear Institute-Organ of Corti 1... 相似文献
58.
59.
Vivian Gedaly-Duff DNSc RN Cathie Burns PhD RN PNP 《Journal of the American Academy of Nurse Practitioners》1992,4(3):95-100
This study used an experimental design to test the question, "Does ice reduce the pain-distress children experience with injections?" One half of the 38 preschool children had ice applied to the preimmunization site for 30 seconds. The remaining children received the injection without the extra intervention. Measures included the Global Mood Scale, pulse rate, Oucher scale, and Faces scale. The results failed to show that ice reduces children's pain-distress with injections. Reasons for the failure are discussed, with comments on the various measures and suggestions for further study in this area of child nursing care. 相似文献
60.