全文获取类型
收费全文 | 906篇 |
免费 | 87篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 27篇 |
妇产科学 | 12篇 |
基础医学 | 159篇 |
口腔科学 | 9篇 |
临床医学 | 114篇 |
内科学 | 173篇 |
皮肤病学 | 16篇 |
神经病学 | 99篇 |
特种医学 | 14篇 |
外科学 | 65篇 |
综合类 | 7篇 |
一般理论 | 4篇 |
预防医学 | 158篇 |
眼科学 | 11篇 |
药学 | 63篇 |
肿瘤学 | 54篇 |
出版年
2024年 | 3篇 |
2023年 | 25篇 |
2022年 | 23篇 |
2021年 | 43篇 |
2020年 | 28篇 |
2019年 | 52篇 |
2018年 | 49篇 |
2017年 | 27篇 |
2016年 | 32篇 |
2015年 | 35篇 |
2014年 | 31篇 |
2013年 | 47篇 |
2012年 | 84篇 |
2011年 | 66篇 |
2010年 | 32篇 |
2009年 | 31篇 |
2008年 | 41篇 |
2007年 | 65篇 |
2006年 | 58篇 |
2005年 | 47篇 |
2004年 | 50篇 |
2003年 | 32篇 |
2002年 | 23篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1995年 | 4篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有993条查询结果,搜索用时 15 毫秒
981.
Background Research indicates that multifaceted practice development (PD) interventions are more effective than single strategies. However, models of education in health care need to consider cost‐effectiveness. Objectives This paper presents a research‐based, PD theory called the Individual Practice Development Theory. It argues that programmes that use the Individual Practice Development Theory to tailor PD support to the learning needs of practitioners will result in more engagement in PD and will target PD resources efficiently. Methods The in‐depth qualitative, multi‐method realistic evaluation was of a multifaceted, organization‐wide PD programme in one National Health Service Mental Health and Learning Disabilities Trust. Semi‐structured interviews, practice observation and documentation audit were used to gather data from occupational therapists. Findings Results indicated that environmental contexts, particularly the support of the immediate team, and the participant's personal circumstances affected PD behaviour change. Six mechanisms acted as catalysts. These were: Building Confidence, Finding Flow, Accumulating Reward, Conferring with Others, Constructing Knowledge Know‐how and Channelling Time. Four stages of PD characterized as: ‘In the Hangar’, ‘On the Runway’, ‘Take‐off’ and ‘In the Air’ were identified. The research also illustrated the interconnectivity between outcome levels, contextual circumstances and activating mechanisms. Discussion The findings suggested that PD interventions need to be more individually tailored to achieve optimum learning outcomes. The identification of four discernable stages permits rapid understanding of PD support needs in order to focus PD support. Conclusion With a systematic and individualized approach to PD in health care, more target PD supports can be put in place. 相似文献
982.
983.
984.
Oestrogen formation and connective tissue growth factor expression in rat granulosa cells 总被引:2,自引:0,他引:2
Ovarian follicular development involves continual remodelling of the extracellular matrix (ECM) forming the basement membrane and intercellular framework that support granulosa cell (GC) growth and differentiation. Insight into the molecular regulation of ovarian ECM remodelling is potentially translatable to tissue remodelling elsewhere in the body. We therefore studied the link between a gene marker of ECM remodelling (connective tissue growth factor (CTGF)) and oestrogen biosynthesis (cytochrome P450(aromatase) (P450(arom))) in rat granulosa cells. To determine if a cause-effect interaction exists, we used semi-quantitative in situ hybridisation to analyse patterns of CTGF and P450(arom) mRNA expression and immunohistochemistry to detect CTGF protein localisation throughout follicular development, and tested the actions of CTGF on oestrogen biosynthesis and oestradiol on CTGF mRNA expression in isolated GC in vitro. CTGF mRNA levels in GC rose gradually through small preantral (SP) and small antral (SA) stages of development to a maximum (fivefold higher) in large antral (LA) follicles. In preovulatory (PO) follicles, the CTGF mRNA level fell to 30% of that in SP follicles. P450(arom) mRNA also increased (threefold in LA relative to SP) throughout antral development follicles, but in contrast to CTGF continued to increase (12-fold) in PO follicles. In the cumulus oophorus of PO follicles, the residual GC CTGF mRNA expression increased with proximity to the oocyte, being inversely related to P450(arom). Elsewhere in the follicle wall, there was a mural-to-antral gradient of CTGF mRNA expression, again inversely related to P450(arom). Immunohistochemistry showed CTGF protein localisation broadly followed mRNA expression during follicular development, although the protein was also present in the theca interna and ovarian surface epithelium. Gradients in CTGF expression across the cumulus oophorus and follicle wall were similar to those observed for mRNA with CTGF protein expression being greatest in proximity to the oocyte. Treatment of isolated GC from preantral and SA follicles with recombinant human CTGF (1-100 ng/ml) did not affect basal or FSH-stimulated GC aromatase activity. However, in the absence of FSH, oestradiol (10(-7)-10(-5) M) stimulated CTGF mRNA expression up to twofold. Conversely, FSH (10 ng/ml) alone reduced CTGF mRNA expression by 40% and combined treatment with FSH and oestradiol further suppressed CTGF to 10% of the control value. The oestrogen receptor (ER) antagonist, ICI 182 780 blocked the stimulatory and inhibitory effects of oestradiol, suggesting a specific ER-mediated mode of action on CTGF. Therefore, CTGF gene expression in GC is under local control by oestrogen whose effect (positive or negative) is modulated by FSH. This helps explain why gene expression of CTGF and P450(arom) diverge in FSH-induced PO follicles and has implications for oestrogenic regulation of CTGF formation elsewhere in the body. 相似文献
985.
Surveillance of mother-to-child transmission prevention programmes at immunization clinics: the case for universal screening 总被引:1,自引:0,他引:1
BACKGROUND: Surveillance programmes for prevention of mother-to-child transmission of HIV (PMTCT) fail to quantify numbers of infant HIV infections averted, often because of poor postnatal follow-up. Additionally, infected infants are often not identified early and only gain access to comprehensive HIV care and treatment late in their disease. METHODS: Anonymous, unlinked, HIV prevalence testing was conducted on dried blood spot (DBS) samples from all infants attending 6 week immunization clinics at seven primary health care clinics offering PMTCT. Samples were tested for HIV antibodies (indicating maternal HIV infection) and those determined to be from HIV-exposed infants were tested for HIV RNA by polymerase chain reaction. Infant and child mortality rates were determined using birth histories. RESULTS: Samples were collected from 2489 infants aged 4-8 weeks. HIV antibodies were identified in 931 infants [37.4%; 95% confidence interval (CI), 35.4-39.4], of whom 188 were HIV RNA positive. The estimated vertical transmission rate (VTR) was 20.2% (95% CI, 17.8-23.1%); 7.5% of all infants at this age were infected. Amongst mothers who reported that they had taken single-dose nevirapine for PMTCT, VTR was 15.0%. Amongst women who reported being HIV uninfected but whose infants had HIV antibodies, VTR was 30.5%. Infant mortality rates in KwaZulu Natal increased from 28/1000 live births in 1990-1994 to 92/1000 in 2000-2004. CONCLUSIONS: Anonymous HIV prevalence screening of all infants at immunization clinics is feasible to monitor the impact of PMTCT programmes on peripartum infection; linked screening could identify infected children early for referral into care and treatment programmes. 相似文献
986.
c-FLIP: a key regulator of colorectal cancer cell death 总被引:4,自引:0,他引:4
Wilson TR McLaughlin KM McEwan M Sakai H Rogers KM Redmond KM Johnston PG Longley DB 《Cancer research》2007,67(12):5754-5762
c-FLIP is an inhibitor of apoptosis mediated by the death receptors Fas, DR4, and DR5 and is expressed as long (c-FLIP(L)) and short (c-FLIP(S)) splice forms. We found that small interfering RNA (siRNA)-mediated silencing of c-FLIP induced spontaneous apoptosis in a panel of p53 wild-type, mutant, and null colorectal cancer cell lines and that this apoptosis was mediated by caspase-8 and Fas-associated death domain. Further analyses indicated the involvement of DR5 and/or Fas (but not DR4) in regulating apoptosis induced by c-FLIP siRNA. Interestingly, these effects were not dependent on activation of DR5 or Fas by their ligands tumor necrosis factor-related apoptosis-inducing ligand and FasL. Overexpression of c-FLIP(L), but not c-FLIP(S), significantly decreased spontaneous and chemotherapy-induced apoptosis in HCT116 cells. Further analyses with splice form-specific siRNAs indicated that c-FLIP(L) was the more important splice form in regulating apoptosis in HCT116, H630, and LoVo cells, although specific knockdown of c-FLIP(S) induced more apoptosis in the HT29 cell line. Importantly, intratumoral delivery of c-FLIP-targeted siRNA duplexes induced apoptosis and inhibited the growth of HCT116 xenografts in BALB/c severe combined immunodeficient mice. In addition, the growth of c-FLIP(L)-overexpressing colorectal cancer xenografts was more rapid than control xenografts, an effect that was significantly enhanced in the presence of chemotherapy. These results indicate that c-FLIP inhibits spontaneous death ligand-independent, death receptor-mediated apoptosis in colorectal cancer cells and that targeting c-FLIP may have therapeutic potential for the treatment of colorectal cancer. 相似文献
987.
Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes 总被引:1,自引:0,他引:1
Tamás P Hawley SA Clarke RG Mustard KJ Green K Hardie DG Cantrell DA 《The Journal of experimental medicine》2006,203(7):1665-1670
The adenosine monophosphate (AMP)-activated protein kinase (AMPK) has a crucial role in maintaining cellular energy homeostasis. This study shows that human and mouse T lymphocytes express AMPKalpha1 and that this is rapidly activated in response to triggering of the T cell antigen receptor (TCR). TCR stimulation of AMPK was dependent on the adaptors LAT and SLP76 and could be mimicked by the elevation of intracellular Ca(2+) with Ca(2+) ionophores or thapsigargin. AMPK activation was also induced by energy stress and depletion of cellular adenosine triphosphate (ATP). However, TCR and Ca(2+) stimulation of AMPK required the activity of Ca(2+)-calmodulin-dependent protein kinase kinases (CaMKKs), whereas AMPK activation induced by increased AMP/ATP ratios did not. These experiments reveal two distinct pathways for the regulation of AMPK in T lymphocytes. The role of AMPK is to promote ATP conservation and production. The rapid activation of AMPK in response to Ca(2+) signaling in T lymphocytes thus reveals that TCR triggering is linked to an evolutionally conserved serine kinase that regulates energy metabolism. Moreover, AMPK does not just react to cellular energy depletion but also anticipates it. 相似文献
988.
OBJECTIVE: There is international recognition that health personnel involved in deliveries should be adequately trained in neonatal resuscitation. A survey was carried out in New South Wales (NSW) and the Australian Capital Territory (ACT) to ascertain the type, frequency and availability of training in neonatal resuscitation to staff who may need to resuscitate an infant at birth. The survey included a self-perception rating of confidence and competence in neonatal resuscitation. METHODS: Questionnaires were sent to 117 hospitals carrying out deliveries in NSW and ACT. Questionnaires were distributed to staff members who may be present at a delivery in a designated 24-h period. RESULTS: In total, 1457 questionnaires from 101 hospitals were returned and analysed. Overall response rate was 86.3% with 96.1% able to be assigned to tertiary, urban non-tertiary or rural areas. Eighty-five per cent of tertiary respondents had a training programme available to them compared with 59% of urban non-tertiary staff and 31% of rural practitioners. Approximately one-third of respondents in rural and urban non-tertiary units had either never been trained or had training more than 2 years before the survey. In rural areas more than 25% staff were not confident in their resuscitation skills and only 9% felt very competent. CONCLUSION: Three-quarters of all births in NSW and ACT take place in rural or urban non-tertiary hospitals where one-third of health personnel are inadequately trained in neonatal resuscitation and many do not feel confident in their skills. Effective neonatal resuscitation training for these areas is urgently required. 相似文献
989.
990.
Rachel Rabin Alireza Radmanesh Ian A. Glass William B. Dobyns Kimberly A. Aldinger Joseph T. Shieh Shelby Romoser Hannah Bombei Leah Dowsett Pamela Trapane John A. Bernat Janice Baker Nancy J. Mendelsohn Bernt Popp Manuela Siekmeyer Ina Sorge Francis Hugh Sansbury Patrick Watts Nicola C. Foulds Jennifer Burton George Hoganson Jane A. Hurst Lara Menzies Deborah Osio Larissa Kerecuk Jan M. Cobben Khadijé Jizi Sebastien Jacquemont Stacey A. Bélanger Katharina Löhner Hermine E. Veenstra‐Knol Henny H. Lemmink Jennifer Keller‐Ramey Ingrid M. Wentzensen Sumit Punj Kirsty McWalter Jerica Lenberg Katarzyna A. Ellsworth Kelly Radtke Schahram Akbarian John Pappas 《American journal of medical genetics. Part A》2020,182(9):2037-2048