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排序方式: 共有2413条查询结果,搜索用时 187 毫秒
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Jennifer C. Sasaki Ashley Allemang Steven M. Bryce Laura Custer Kerry L. Dearfield Yasmin Dietz Azeddine Elhajouji Patricia A. Escobar Albert J. Fornace Jr Roland Froetschl Sheila Galloway Ulrike Hemmann Giel Hendriks Heng-Hong Li Mirjam Luijten Gladys Ouedraogo Lauren Peel Stefan Pfuhler Daniel J. Roberts Véronique Thybaud Jan van Benthem Carole L. Yauk Maik Schuler 《Environmental and molecular mutagenesis》2020,61(1):114-134
In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc. 相似文献
3.
Richard B Thompson Ewout J van den Bos Bryce H Davis Yoshihisa Morimoto Damian Craig Brad S Sutton Donald D Glower Doris A Taylor 《The Journal of heart and lung transplantation》2005,24(2):205-214
BACKGROUND: Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells. METHODS: Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically. RESULTS: All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype. CONCLUSIONS: Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction. 相似文献
4.
HJ Aubin S Tilikete C Laureaux HT Nguyen Hac MC Roullet-Volmi S Troupel D Barrucand 《European psychiatry》1995,10(8)
The aim of this study was to assess alcoholic inpatients' smoking and coffee intake variation following withdrawal. Only moderate smokers (less than 30 cigarettes/day) showed a significant increase of cigarette consumption after alcohol withdrawal. However, their urinary cotinine level did not vary, suggesting a behavioral, and not biological, compensation through smoking following alcohol withdrawal. Heavy smokers (30 cigarettes/day or more) showed no significant clinical or biological variation of smoking behavior. Coffee consumption increased after alcohol withdrawal in all patients, irrespective of smoking habits. 相似文献
5.
Reeve Bryce B. Hays Ron D. Chang Chih-Hung Perfetto Eleanor M. 《Quality of life research》2007,16(1):1-8
Background Health-related quality of life (HRQL) is an accepted outcome measure in patients with mood and anxiety disorders. Yet, surprisingly
little attention has been paid to the determinants. In this paper we test the hypothesis that it is associated with personality
traits while controlling for mental disorders.
Methods A large sample of outpatients (n=640) with mood and anxiety disorders was studied. The empirically supported five factor model
of normal personality traits was assessed using the NEO-FFI and includes: neuroticism, extraversion, openness to experience,
agreeableness, and conscientiousness. Mental disorders were assessed with the CIDI, and HRQL with the SF-36.
Results Regression analyses revealed that the NEO-FFI scores, with the exception of conscientiousness, were significantly associated
with SF-36 subscales and summary scores, independently from the mental disorders. The percentage of explained variance due
to the personality traits was highest for the subscales Vitality (10.0%), Mental Health (13.3%) and the Mental Health Summary
Score (9.5%). Furthermore, specific personality traits were related to specific SF-36 subscales.
Conclusions A low HRQL of patients with mood or anxiety disorders is not only determined by the disease or the current health but is also
shaped by personality traits that are relatively stable throughout an individual's life time. 相似文献
6.
Suzie Bryce Tim Rowse David Scrimgeour 《Australian and New Zealand journal of public health》1992,16(4):387-396
Abstract: The evaluation of the Healthy Aboriginal Life Team's (HALT) petrol-sniffing prevention programs at Yuendumu, Kintore and the Pitjantjatjara Lands first required a specification of program outcome—which was not changes in the enumerated prevalence of petrol sniffing, but alteration in parental perceptions of the relevance and effectiveness of families' nurturant authority over recalcitrant youngsters. The evaluation then proceeded by a series of interviews with resident or ex-resident adults (Aboriginal and non-Aboriginal) of Yuendumu, Kintore, Kiwirrkurra, Ernabella, Indulkana and Fregon. Adults articulated their efficacy in different ways in each place. Some favoured the conclusion that HALT had helped them, others clearly identified HALT as an obstacle to or a distraction from the implementation of other preventive and curative community-based action. We discerned a ferment of cultural adjustment in the distribution of authority over children among parents and welfare agencies. We caution against finding in HALT'S successes a model procedure for benign interventions into such cultural adjustment. 相似文献
7.
BACKGROUND: A simple, rapid, inexpensive method for measuring the flow in a
patient's vascular access would permit routine monitoring during
haemodialysis, and hence provide information of access graft deterioration
sufficiently early to increase the success of minimally invasive remedial
procedures. This paper reports the validation of such a method in animals.
METHODS: A PTFE graft was implanted in sheep between the carotid artery and
the jugular vein. While the sheep was under general anaesthesia and on an
haemodialysis circuit, ultrasound velocity in its blood was perturbed by
the injection of a 5-10 ml bolus of isotonic NaCl. The pump tubing flow was
measured by a transit-time blood flow meter. This flow was combined with
the areas of perturbation generated by the injection before and after
mixing in the access flow to estimate graft flow. The calculated graft flow
was compared to flow measured directly by a transit-time probe on the same
carotid artery. RESULTS: Over a 10-fold range, 120-1260 ml/min, graft flow
measured by ultrasound velocity dilution agreed well with graft flow
measured directly with a scatter of 76 ml/min about the regression line.
CONCLUSION: Ultrasound velocity dilution provides a method for measuring
flow in the graft accurate enough for clinical evaluation of patients on
dialysis.
相似文献
8.
9.
What Is Sufficient Evidence for the Reliability and Validity of Patient-Reported Outcome Measures? 总被引:1,自引:0,他引:1
10.
Robert A Budinsky Dennis Paustenbach Donald Fontaine Bryce Landenberger Thomas B Starr 《Toxicological sciences》2006,91(1):275-285
The recent National Toxicology Program (NTP) cancer bioassays for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) permit a reevaluation of the current TEF value of 4-PeCDF. The data also allow for the derivation of relative potency factors (RPFs) for cancer, which are based not only on administered dose but also on potentially more informative dose metrics, such as liver concentration, area under the liver concentration curve, and lifetime average body burden. Our analyses of these data indicate that chi-squared tests of observed versus predicted liver tumor incidence for 4-PeCDF reject the current TEF value of 0.5 value as too high. 4-PeCDF RPFs were derived using estimation methods that either did or did not assume parallelism of the 4-PeCDF and TCDD dose-response curves. The resulting parallelism-based RPFs for administered dose, liver concentration at terminal sacrifice, liver concentration AUC, and lifetime average body burden are 0.26, 0.014, 0.021, and 0.036, respectively. The administered dose RPF estimate is approximately one-half the current TEF value of 0.5. However, the use of administered dose fails to take into account pharmacokinetic differences between congeners and the generally acknowledged belief that body burden or some other measure of cumulative dose is more appropriate for estimating the health risk posed by persistent chemicals. The other three dose metrics do account for these important factors, and the corresponding RPFs are at least 10-fold lower than the current TEF for 4-PeCDF. In summary, our analyses support an administered dose TEF no greater than 0.25 and one in the 0.05-0.1 range for internal dose metrics such as lifetime average liver concentration or body burden. 相似文献