全文获取类型
收费全文 | 204篇 |
免费 | 6篇 |
专业分类
耳鼻咽喉 | 4篇 |
妇产科学 | 16篇 |
基础医学 | 36篇 |
临床医学 | 10篇 |
内科学 | 21篇 |
皮肤病学 | 13篇 |
神经病学 | 9篇 |
特种医学 | 5篇 |
外科学 | 6篇 |
预防医学 | 7篇 |
眼科学 | 1篇 |
药学 | 16篇 |
肿瘤学 | 66篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 5篇 |
2014年 | 7篇 |
2013年 | 11篇 |
2012年 | 9篇 |
2011年 | 8篇 |
2010年 | 8篇 |
2009年 | 4篇 |
2008年 | 9篇 |
2007年 | 11篇 |
2006年 | 14篇 |
2005年 | 9篇 |
2004年 | 17篇 |
2003年 | 14篇 |
2002年 | 18篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1908年 | 1篇 |
排序方式: 共有210条查询结果,搜索用时 15 毫秒
1.
High-efficiency gene transfer to primary T lymphocytes by recombinant adenovirus vectors 总被引:3,自引:0,他引:3
Zhi Chen Matti Ahonen Heli Hmlinen Jeffrey M. Bergelson Veli-Matti Khri Riitta Lahesmaa 《Journal of immunological methods》2002,260(1-2):79-89
Recombinant, replication-deficient adenoviruses are efficient vectors for gene transfer to a wide range of cell types, with the exception of T lymphocytes. Here, we show that primary T lymphocytes from peripheral blood, cord blood, and the Jurkat T cell line are efficiently transduced by recombinant adenovirus. Nearly 100% infection efficiency of primary T cells is obtained with high multiplicity of infection (MOI) (5000) of recombinant adenovirus coding for lacZ. Similar infection efficiency by adenovirus-mediated gene transfer was obtained at lower MOI (3000) by activating primary T cells with PHA and PMA. Addition of cationic liposomes together with RAdlacZ markedly enhanced the infection efficiency at lower MOI (1000) resulting in over 90% infection efficiency. Primary T cells express low levels of coxsackievirus and adenovirus receptor (CAR), a cell surface receptor for adenovirus fiber attachment, as well as vβ3 and vβ5 integrins, cellular receptors for adenovirus internalization. This suggests that adenovirus entry to T cells at high MOI is mediated by other mechanisms. In conclusion, these results demonstrate that genes can be efficiently transferred to primary lymphocytes by adenovirus vectors at high MOI or in combination with cationic liposomes. 相似文献
2.
3.
Minna Taskinen Esa Jantunen Veli-Matti Kosma Petri Bono Marja-Liisa Karjalainen-Lindsberg Sirpa Leppä 《European journal of cancer (Oxford, England : 1990)》2010,46(13):2506-2512
BackgroundTumour-infiltrating mast cells (MCs) can remodel tumour microenvironment and growth by suppressing immune responses and potentiating angiogenesis. Furthermore, accumulation of MCs in follicular lymphoma (FL) correlates with unfavourable prognosis after immunochemotherapy. Here we investigated whether tumour vascularity is associated with MC content and outcome in FL patients treated with immunochemotherapy.Patients and methodsMicrovessel density (MVD) and MC content were determined immunohistochemically from pretreatment samples of 95 FL patients using CD31, CD34 and mast cell tryptase antibodies. Gene expression data from a separate set of 24 FL patients were analysed for comparison. All patients were treated with the combination of rituximab (R) and cyclophoshamide-doxorubicin–vincristine–prednisone (CHOP) chemotherapy.ResultsIncreased CD31+ MVD correlated positively with the number of tumour infiltrating MCs and CD34+ vessels, and negatively with the outcome. Overall survival and progression-free survival were significantly better among patients with low CD31+ MVDs. In multivariate analyses, CD31+ MVD had prognostic value independently of Follicular Lymphoma Prognostic Index but not of MC content. Consistent with the immunohistochemical data, high CD31/PECAM1 mRNA levels were associated with adverse outcome. Conversely, a positive prognostic impact of VEGF mRNA expression on the outcome was found.ConclusionVascularity is associated with MC content and outcome in R-CHOP-treated FL patients. 相似文献
4.
Emilia A. Korhonen Aino Murtomki Sawan Kumar Jha Andrey Anisimov Anne Pink Yan Zhang Simon Stritt Inam Liaqat Lukas Stanczuk Laura Alderfer Zhiliang Sun Emmi Kapiainen Abhishek Singh Ibrahim Sultan Anni Lantta Veli-Matti Leppnen Lauri Eklund Yulong He Hellmut G. Augustin Kari Vaahtomeri Pipsa Saharinen Taija Mkinen Kari Alitalo 《The Journal of clinical investigation》2022,132(15)
Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C–induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110α subunit or with small-molecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C–induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling. 相似文献
5.
Hanna Jantunen Niko Wasenius Minna K. Salonen Hannu Kautiainen Mikaela B. von Bonsdorff Eero Kajantie Johan G. Eriksson 《Scandinavian journal of medicine & science in sports》2019,29(11):1797-1804
The aim of the study was to examine the association between change in leisure‐time physical activity (LTPA) and change in health‐related quality of life (HRQoL) and symptoms of depression during a 10‐year follow‐up. This prospective study included 1036 men and women (mean age at baseline = 61.2 years) from the Helsinki Birth Cohort Study. Leisure‐time physical activity was measured with a questionnaire, HRQoL with SF36 and depression symptoms with Beck's depression inventory (BDI). The association between the change in LTPA and change in HRQoL and BDI were investigated with sex‐stratified general linear models adjusted for age, smoking, educational attainment, comorbidity score, and baseline value of outcomes. One standard deviation (SD) increase in LTPA was associated with increase in physical summary component of HRQoL in women (B = 0.7 unit, 95% CI = 0.1‐1.3, P = 0.032) and in men (B = 0.8 unit, 95% CI = 0.2‐1.5, P = 0.014). In women, the 1SD increase in LTPA was also associated with an increase in mental summary component score (B = 1.0, 95% CI = 0.3‐1.7, P = 0.005) and a reduction in depressive symptoms (B = ?0.7, 95% CI = ?1.1 to ?0.2, P = 0.003). In conclusion, increase in the volume of LTPA over a 10‐year period in late adulthood was associated with improved HRQoL in both men and women, and also diminished depressive symptoms in women. The findings support the promotion of physical activity in later years to enhance HRQoL and mental well‐being. 相似文献
6.
Pukkila M Kosunen A Ropponen K Virtaniemi J Kellokoski J Kumpulainen E Pirinen R Nuutinen J Johansson R Kosma VM 《Journal of clinical pathology》2007,60(3):267-272
BACKGROUND: Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour growth. AIMS: To investigate whether the versican expression level in the peritumoural stromal tissue of primary oral squamous cell carcinoma (OSCC) predicts relapse-free or disease-specific survival. Also, to study the associations between versican expression and several other clinicopathological variables, as well as tumour cell proliferation. METHODS: Immunohistochemistry was used to study the expression of versican and tumour cell proliferative activity in 139 OSCCs. All pertinent clinical data were collected retrospectively from the hospital records. RESULTS: In this cohort, versican expression did not correlate with the clinicopathological factors or tumour cell proliferation. In univariate analyses, higher risk for disease recurrence was associated with higher stromal versican expression score (p = 0.02), positive neck node status (p = 0.02), lower Karnofsky performance status (p = 0.03) and higher tumour cell proliferation index (p = 0.04). Increased disease-specific risk of death was associated with high stromal versican expression score (p = 0.005) higher T class (p = 0.002), positive neck node status (p<0.001), higher stage (p<0.001), poorer histological differentiation (p = 0.005), worse general condition of the patient (p = 0.049) and increased tumour cell proliferative index (p = 0.02). In multivariate disease-specific survival analysis, high stromal versican expression score (p = 0.048), poorer histological differentiation (p = 0.047) and higher stage (p = 0.002) independently predicted poorer disease outcome. CONCLUSIONS: In this cohort, increased stromal versican expression correlated with both increased risk for disease recurrence and shortened survival. High stromal versican expression may thus be considered an independent and adverse prognostic marker in OSCC. 相似文献
7.
Frej Stenbck Veli-Matti Wasenius 《European journal of obstetrics, gynecology, and reproductive biology》1985,20(6):357-371
The location and amount of the basement membrane (BM) components collagen IV and laminin were studied in ovarian epithelial, sex cord-stromal and germ cell tumors. BM structures were found in the epithelial stromal interface of benign surface epithelial tumors and, though discontinuous, around well-differentiated tumor islets, being less well developed in invasive undifferentiated neoplasms. The stromal components in Müllerian mixed tumors had less distinct BM structures, a finding useful for the classification of these neoplasms. Thecomas and fibromas had scanty collagen IV and laminin; granulosa cell tumors contained large amounts of BM material. A fine diffuse BM-positive pattern occurred in dysgerminomas and endodermal sinus tumors; BM structures in cystic teratomas were distinct. Collagen IV and laminin were well-developed in benign and slow-growing tumors with epithelial components and in their metastases, but less distinct in stromal tumors and highly malignant undifferentiated tumors, showing the usefulness of this method for the clinical and biological classification of such tumors. 相似文献
8.
Low-molecular-weight (LMW) heparins have been shown to be at least as effective as unfractionated (UF) heparin in the treatment of deep venous thrombosis (DVT) in nonpregnant subjects. LMW heparins have been shown to be safe when used during pregnancy as they do not cross the placenta. Up to now, they have been used mainly in thromboprophylaxis during pregnancy and rarely in the treatment of acute DVT in pregnant women. In a prospective observational study, we compared the effectiveness and safety of the LMW heparin, dalteparin, with UF heparin in the initial treatment (first week) of DVT during pregnancy. After confirmation of DVT by ultrasonography, 10 women were treated with UF heparin (25,430 IU/day, mean) and 21 women with dalteparin (16,000 IU/day, mean) for 7 days and, thereafter, all women were given treatment doses of LMW heparin for another 2 weeks. The dose was then gradually decreased and kept at a high prophylactic dose until delivery. One patient in the dalteparin group had recurrence of DVT 2 weeks after starting the treatment. No differences were observed between the groups in symptoms or bleeding complications during pregnancy and delivery. Our results indicate that LMW heparin is as effective and safe as UF heparin for the first week of treatment, but LMW heparin has the advantage of being easily administered and few laboratory controls are required. 相似文献
9.
10.
Sillanpää P Hirvonen A Kataja V Eskelinen M Kosma VM Uusitupa M Vainio H Mitrunen K 《Pharmacogenetics》2004,14(4):239-245
The association between vitamin D receptor (VDR) gene polymorphisms and diseases such as breast cancer, prostate cancer and osteoporosis has been extensively investigated during recent years. To date, several polymorphisms have been found in the VDR gene. In this Finnish case-control study, comprising 483 breast cancer patients and 482 healthy population controls, we investigated the association between altered breast cancer risk and two polymorphisms in the 3' end of the gene detectable with ApaI and TaqI restriction enzymes. A statistically significant difference was observed in the ApaI genotype distribution between cases and controls. Women with the VDR variant a allele containing genotypes showed a decreased risk for breast cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.54-0.98] compared to women with the AA genotype. This association was especially strong among women with a positive family history of breast cancer (OR 0.14, 95% CI 0.03-0.76). Moreover, there was a trend (P for trend = 0.0007) for decreased risk with increasing number of variant alleles. The lowest risk of breast cancer was seen for the women with the aa genotype (OR 0.03, 95% CI 0.003-0.31) compared to women with the AA genotype. A tendency of decreased risk of breast cancer was also observed for the TaqI T allele containing genotypes (Tt and TT) (OR 0.68, 95% CI 0.41-1.12), but because the distribution of Taql alleles in the controls missed the Hardy-Weinberg equilibrium (P = 0.01), we were unable to properly assess the potential impact of the TaqI polymorphism in breast cancer susceptibility. In conclusion, our results suggest that the VDR ApaI genotype may be an important modifier of individual breast cancer risk among Finnish women, especially if they have a positive family history of breast cancer. 相似文献