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91.
Sean C. Skeldon Kara Semotiuk Melyssa Aronson Spring Holter Steven Gallinger Aaron Pollett Cynthia Kuk Bas van Rhijn Peter Bostrom Zane Cohen Neil E. Fleshner Michael A. Jewett Sally Hanna Shahrokh F. Shariat Theodorus H. Van Der Kwast Andrew Evans Jim Catto Bharati Bapat Alexandre R. Zlotta 《European urology》2013
Background
Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse.Objective
To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations.Design, setting, and participants
Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2).Outcome measurements and statistical analysis
Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors.Results and limitations
Eleven of 177 patients with MSH2 mutations (6.21%, p < 0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p > 0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p < 0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias.Conclusions
LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening. 相似文献92.
Benjamin D. Aronson Kristin K. Janke 《Research in social & administrative pharmacy》2018,14(7):678-685
Background
Professional engagement has importance to the professional of pharmacy, and in particular the growth of student pharmacists. Measurement of this construct would allow investigation of factors that may increase or decrease professional engagement.Objectives
To describe the development of the Student Pharmacist Inventory of Professional Engagement (S-PIPE), assess the factor structure and convergent validity, and test for differences in professional engagement based upon demographic and background factors.Methods
Potential items for the S-PIPE were developed iteratively through inductive and deductive item-writing, 2 pilot administrations, expert review of items, and assessment of the content validity index, and cognitive interviews with students. The S-PIPE was administered to a cohort of 164 first year student pharmacists at University of Minnesota, along with items querying types and level of involvement in professional experiences and activities. An exploratory factor analysis was conducted using principal axis factoring extraction and Promax rotation. The number of factors to retain was based upon eigenvalues, examination of the scree plot, and a parallel analysis. Factors of the S-PIPE were compared to self-rated level of involvement and other demographic factors.Results
Three factors were retained accounting for 70.7% of the variance, and named Belonging (α = 0.942, 9 items), Connectedness (α = 0.864, 3 items), and Meaningful Experience (α = 0.760, 4 items). All 3 factors were significantly correlated to self-rated involvement (r = 0.291 to 0.370). Level of professional engagement differed in this study by gender, and pharmacy work experience.Conclusions
This study lays the foundation for quantitative research in professional engagement among student pharmacists. Future work is needed to further validate and extend these findings. 相似文献93.
Kimo C. Stine Elizabeth C. Wahl Lichu Liu Robert A. Skinner Jacquelyn VanderSchilden Robert C. Bunn Corey O. Montgomery Larry J. Suva James Aronson David L. Becton Richard W. Nicholas Christopher J. Swearingen Charles K. Lumpkin Jr. 《Journal of orthopaedic research》2014,32(3):464-470
Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non‐cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five‐dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five‐dose CDP regimen were observed in TNFR1KO mice. The two‐dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri‐operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:464–470, 2014. 相似文献
94.
In this case, a male patient presented with a clinically and radiographieally unstable slipped capital femoral epiphysis (SCFE) as well as slipped calcaneal epiphysis years. Subsequent thorough at the age of 23 work-up revealed that he had some features of rickets and labo- ratory test demonstrated he had hypophos- phatemia (2.3mg/dl), normocalcemia, normal vi- tamin D metabolite levels, and secondary hy- perparathyroidism. 相似文献
95.
96.
Jane E Sarginson JF William Deakin Ian M Anderson Darragh Downey Emma Thomas Rebecca Elliott Gabriella Juhasz 《Neuropsychopharmacology》2014,39(12):2857-2866
There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual''s susceptibility to depression. 相似文献
97.
Diverse HIV-1 subtypes and clinical, laboratory and behavioral factors in a recently infected US military cohort 总被引:5,自引:0,他引:5
98.
Arthur I. Aronson Fred H. Wilt 《Proceedings of the National Academy of Sciences of the United States of America》1969,62(1):186-193
Pulse-labeled RNA in early sea urchin embryos (64 cells to mesenchyme blastulase) is found almost exclusively associated with the nucleus and turns over very rapidly. The rate of labeling of the cytoplasm is much slower and is consistent with the transfer of 6 per cent of the nuclear RNA made every 15-20 minutes. Most of the pulse-labeled nuclear RNA exists in membrane-bound polyribosomes. 相似文献
99.
Bishop JF; Matthews JP; Young GA; Szer J; Gillett A; Joshua D; Bradstock K; Enno A; Wolf MM; Fox R 《Blood》1996,87(5):1710-1717
High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3-7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7-3-7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5-2-5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC- 3-7 and 74% with 7-3-7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3-7 and 12 months with 7-3- 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3-7 and 24% on 7-3-7. Patients in CR tended to survive longer with HIDAC-3-7 but there were no overall survival differences between the two arms. HIDAC-3-7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7-3-7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3-7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC- 3-7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML. 相似文献
100.
Yves?JF?GarinEmail author Pascale?Meneceur Francine?Pratlong Jean-Pierre?Dedet Francis?Derouin Frédéric?Lorenzo 《BMC infectious diseases》2005,5(1):18