全文获取类型
收费全文 | 964篇 |
免费 | 78篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 67篇 |
妇产科学 | 13篇 |
基础医学 | 111篇 |
口腔科学 | 25篇 |
临床医学 | 155篇 |
内科学 | 193篇 |
皮肤病学 | 11篇 |
神经病学 | 74篇 |
特种医学 | 17篇 |
外科学 | 109篇 |
综合类 | 6篇 |
预防医学 | 78篇 |
眼科学 | 12篇 |
药学 | 85篇 |
肿瘤学 | 83篇 |
出版年
2024年 | 4篇 |
2023年 | 11篇 |
2022年 | 21篇 |
2021年 | 31篇 |
2020年 | 29篇 |
2019年 | 42篇 |
2018年 | 35篇 |
2017年 | 27篇 |
2016年 | 33篇 |
2015年 | 34篇 |
2014年 | 43篇 |
2013年 | 67篇 |
2012年 | 55篇 |
2011年 | 62篇 |
2010年 | 39篇 |
2009年 | 42篇 |
2008年 | 61篇 |
2007年 | 72篇 |
2006年 | 58篇 |
2005年 | 54篇 |
2004年 | 49篇 |
2003年 | 35篇 |
2002年 | 38篇 |
2001年 | 14篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有1043条查询结果,搜索用时 15 毫秒
991.
Anthropogenic chemicals released into the environment may have so-called endocrine disruptive effects. For instance, innumerous observations on subtle alterations of fish reproductive systems have been published in the scientific literature during the last decades. At the same time, the evidence is scarce regarding similar effects in crustaceans, which is probably related to the limited understanding of basic crustacean endocrine systems and pathways, rather than absence of endocrine disruption within the crustacean subphylum. This knowledge gap is particularly evident in micro-crustacean species, which are frequently used in environmental risk assessment of chemicals, and adequate tools for identification of potential endocrine disrupters are missing in current chemicals regulation. The main objective of the current study was therefore to utilize an enzyme immunoassay to establish a stable protocol for analysis of individual ecdysteroid levels in the benthic harpacticoid copepod Nitocra spinipes, a species which has been used in ecotoxicological investigations for more than 30 years. Further, to assess the usefulness of the individual ecdysteroid level as a stressor endpoint, it was integrated with a growth-related stressor endpoint battery, i.e. individual RNA content, mean development times, and growth rate, by exposing individual N. spinipes to the insecticide and known ecdysteroid antagonist lindane at 25-400 microg L(-1). The results showed that the ecdysteroid levels were significantly different from the control (71 pg individual(-1)) in the 100 microg L(-1) treatment (124 pg individual(-1)). Although the ecdysteroid levels were not significantly different from the control in the 25-50 microg L(-1) treatments (83-93 pg individual(-1)), these results still show a clear concentration-related trend. In the 200 microg L(-1) treatment, the ecdysteroid content was the highest (165 pg individual(-1)), however not significantly different from the control due to high variation. The 400 microg L(-1) treatment resulted in lowered ecdysteroid levels (107 pg individual(-1)), indicating a profound lindane-induced stress, which was confirmed by high mortality in the same treatment (79%). For all other endpoints there were clear concentration-related effects of lindane, with development time and growth rate as the most sensitive endpoints. In conclusion, this study presents for the first time a tool for identification of endocrine alterations in N. spinipes. By using the established enzyme immunoassay protocol, we obtained individual ecdysteroid levels that integrated well with the growth-related stressor endpoints previously used on this species. 相似文献
992.
Elsherbiny DA Asimus SA Karlsson MO Ashton M Simonsson US 《Journal of pharmacokinetics and pharmacodynamics》2008,35(2):203-217
The study aim was to assess the inductive properties of artemisinin antimalarials using mephenytoin as a probe for CYP2B6 and CYP2C19 enzymatic activity. The population pharmacokinetics of S-mephenytoin and its metabolites S-nirvanol and S-4'-hydroxymephenytoin, including enzyme turn-over models for induction, were described by nonlinear mixed effects modeling. Rich data (8-16 samples/occasion/subject) were collected from 14 healthy volunteers who received mephenytoin before and during ten days of artemisinin administration. Sparse data (3 samples/occasion/subject) were collected from 74 healthy volunteers who received mephenytoin before, during and after five days administration of artemisinin, dihydroartemisinin, arteether, artemether or artesunate. The production rate of CYP2B6 was increased 79.7% by artemisinin, 61.5% by arteether, 76.1% by artemether, 19.9% by dihydroartemisinin and 16.9% by artesunate. The production rate of CYP2C19 increased 51.2% by artemisinin, 14.8% by arteether and 24.9% by artemether. In conclusion, all studied artemisinin derivatives induced CYP2B6. CYP2C19 induction by arteether and artemether as well as CYP2B6 and CYP2C19 induction by artemisinin was confirmed. The inductive capacity is different among the artemisinin drugs, which is of importance when selecting drugs to be used in antimalarial combination therapy such that the potential for drug-drug interactions is minimized. 相似文献
993.
AbstractBackground: Cognitive functioning may have implications for engagement in daily occupations among people with schizophrenia.Objectives: This cross-sectional study explores relationships between time use assessed occupational engagement and cognitive functioning among persons with schizophrenia.Methods: Thirty-nine participants from four mental health care services in Sweden participated. The Profile of Occupational Engagement among persons with Severe mental illness (POES) and a cognitive test battery was used.Results: Higher attention and psychomotor speed and higher scores in information processing speed, immediate and delayed verbal recall, and immediate and delayed visual recall were significantly correlated with higher scores in occupational engagement. Regression analyzes revealed that information processing speed and delayed visual recall best explained the variance in occupational engagement (R2?=?0.36).Conclusions: Cognitive functioning has implications for occupational engagement, and thus the ability to perform daily occupations in a balanced rhythm within various social and physical environments. 相似文献
994.
995.
Jennifer Viberg Johansson Pär Segerdahl Ulrika Hösterey Ugander Mats G. Hansson Sophie Langenskiöld 《Patient education and counseling》2018,101(3):422-427
Objective
It is well known that research participants want to receive genetic risk information that is about high risks, serious diseases and potential preventive measures. The aim of this study was to explore, by qualitative means, something less well known: how do healthy research participants themselves make sense of genetic risk information?Method
A phenomenographic approach was chosen to explore research participants’ understanding and assessment of genetic risk. We conducted four focus-group (N = 16) interviews with participants in a research programme designed to identify biomarkers for cardiopulmonary disease.Results
Among the research participants, we found four ways of understanding genetic risk: as a binary concept, as an explanation, as revealing who I am (knowledge of oneself) and as affecting life ahead.Conclusion
Research participants tend to understand genetic risk as a binary concept. This does not necessarily imply a misunderstanding of, or an irrational approach to, genetic risk. Rather, it may have a heuristic function in decision-making.Practical implications
Risk communication may be enhanced by tailoring the communication to the participants’ own lay conceptions. For example, researchers and counselors should address risk in binary terms, maybe looking out for how individual participants search for threshold figures. 相似文献996.
Hernberg M Mattila PS Rissanen M Hansson J Aamdal S Bastholt L von der Maase H Schmidt H Stierner U Tarkkanen J 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2007,30(7):773-779
The aim of this study was to investigate whether the profile of peripheral blood lymphocyte subsets of patients with high-risk malignant melanoma is associated with prognosis. Blood samples were systematically obtained from 31 patients with high-risk melanoma eligible for the Nordic Melanoma Cooperative Group adjuvant interferon study. The frequencies of peripheral blood lymphocyte subsets were monitored by flow cytometry using CD3, CD4, CD8, CD56, and CD69 monoclonal antibodies. Patients with low proportions of CD3+CD4+CD69+ cells and of CD3+CD56+ cells before treatment had an improved disease-free survival compared to those with high proportions [77.7 vs. 16.8 mo, hazard ratio (HR) 0.25, confidence interval (CI) 0.09-0.71, P=0.005 and 77.2 vs. 16.0 mo, HR: 0.25, CI 0.086-0.73, P=0.001, respectively]. Low pretreatment levels of these cell populations also correlated with a better overall survival (79.2 vs. 22.6 mo, HR: 0.17, CI 0.05-0.52, P=0.0005 and 78.2 vs. 21.4 mo, HR: 0.2, CI 0.07-0.59, P=0.001, respectively). In the multivariate analysis both the pretreatment proportion of CD3+CD4+CD69+ cells (P=0.01, HR: 0.21, CI 0.07-0.67) and CD3+CD56+ cells (P=0.01, HR: 0.22, CI 0.062-0.65) were independent prognostic factors for overall survival. Our data show that both the proportions of CD3+CD4+CD69+ cells and of CD3+CD56+ cells seem to have a prognostic potential in the natural course of melanoma. These results need to be confirmed in larger studies. 相似文献
997.
Sjögren Hannah Pahlm Ulrika Engblom Henrik Erlinge David Heiberg Einar Arheden Håkan Carlsson Marcus Ostenfeld Ellen 《The international journal of cardiovascular imaging》2022,38(2):375-387
The International Journal of Cardiovascular Imaging - To assess (1) global longitudinal strain (GLS) by feature tracking cardiac magnetic resonance (CMR) in the sub-acute and chronic phases after... 相似文献
998.
Anna E Börjesson Helen H Farman Cecilia Engdahl Antti Koskela Klara Sjögren Jenny M Kindblom Alexandra Stubelius Ulrika Islander Hans Carlsten Maria Cristina Antal Andrée Krust Pierre Chambon Juha Tuukkanen Marie K Lagerquist Sara H Windahl Claes Ohlsson 《Journal of bone and mineral research》2013,28(5):1117-1126
Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)‐α. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a nonfunctional ERα had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ERα for the effects of E2 and selective estrogen receptor modulators (SERMs) on bone mass in males. Three mouse models lacking either ERαAF‐1 (ERαAF‐10), ERαAF‐2 (ERαAF‐20), or the total ERα (ERα?/?) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, whereas it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ERα?/? or ERαAF‐20 mirx ERαAF‐10 mice were tissue‐dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERαAF‐1 for the effects of SERMs, we treated orx WT and ERαAF‐10 mice with raloxifene (Ral), lasofoxifene (Las), bazedoxifene (Bza), or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency toward increased cortical bone parameters. Importantly, all SERM effects were absent in the orx ERαAF‐10 mice. In conclusion, ERαAF‐2 is required for the estrogenic effects on all evaluated parameters, whereas the role of ERαAF‐1 is tissue‐specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERαAF‐1. Our findings might contribute to the development of bone‐specific SERMs in males. © 2013 American Society for Bone and Mineral Research. 相似文献
999.
Anna Jonsson Claes Ladenvall Tarunveer Singh Ahluwalia Jasmina Kravic Ulrika Krus Jalal Taneera Bo Isomaa Tiinamaija Tuomi Erik Renstr?m Leif Groop Valeriya Lyssenko 《Diabetes》2013,62(8):2978-2983
Although meta-analyses of genome-wide association studies have identified >60 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes and/or glycemic traits, there is little information on whether these variants also affect α-cell function. The aim of the current study was to evaluate the effects of glycemia-associated genetic loci on islet function in vivo and in vitro. We studied 43 SNPs in 4,654 normoglycemic participants from the Finnish population-based Prevalence, Prediction, and Prevention of Diabetes-Botnia (PPP-Botnia) Study. Islet function was assessed, in vivo, by measuring insulin and glucagon concentrations during oral glucose tolerance test, and, in vitro, by measuring glucose-stimulated insulin and glucagon secretion from human pancreatic islets. Carriers of risk variants in BCL11A, HHEX, ZBED3, HNF1A, IGF1, and NOTCH2 showed elevated whereas those in CRY2, IGF2BP2, TSPAN8, and KCNJ11 showed decreased fasting and/or 2-h glucagon concentrations in vivo. Variants in BCL11A, TSPAN8, and NOTCH2 affected glucagon secretion both in vivo and in vitro. The MTNR1B variant was a clear outlier in the relationship analysis between insulin secretion and action, as well as between insulin, glucose, and glucagon. Many of the genetic variants shown to be associated with type 2 diabetes or glycemic traits also exert pleiotropic in vivo and in vitro effects on islet function.In the last few years, genome-wide association studies have substantially increased the knowledge of genetic variants predisposing to type 2 diabetes. Although the majority of these single nucleotide polymorphisms (SNPs) seem to influence insulin secretion, few, if any, studies have assessed their simultaneous effects on β- and α-cell function in vivo and in vitro. The aim of the current study was to provide a comprehensive evaluation of the effects of genetic loci associated with type 2 diabetes (1) and/or glucose and insulin levels (2) on islet function in vivo, in a large well-characterized population-based study from the western coast of Finland (the Prevalence, Prediction, and Prevention of Diabetes-Botnia [PPP-Botnia] Study), and in vitro, in human pancreatic islets. Islet function was assessed by measuring insulin and glucagon concentrations during an oral glucose tolerance test (OGTT). 相似文献
1000.