全文获取类型
收费全文 | 187篇 |
免费 | 7篇 |
专业分类
儿科学 | 13篇 |
基础医学 | 30篇 |
临床医学 | 13篇 |
内科学 | 48篇 |
皮肤病学 | 2篇 |
神经病学 | 5篇 |
特种医学 | 6篇 |
外科学 | 10篇 |
预防医学 | 6篇 |
药学 | 7篇 |
中国医学 | 1篇 |
肿瘤学 | 53篇 |
出版年
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 6篇 |
2013年 | 2篇 |
2012年 | 5篇 |
2011年 | 16篇 |
2010年 | 1篇 |
2009年 | 5篇 |
2008年 | 10篇 |
2007年 | 8篇 |
2006年 | 20篇 |
2005年 | 16篇 |
2004年 | 18篇 |
2003年 | 19篇 |
2002年 | 20篇 |
2001年 | 2篇 |
2000年 | 7篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1981年 | 2篇 |
排序方式: 共有194条查询结果,搜索用时 15 毫秒
51.
Expression of CD34 in pulmonary endothelial cells in vivo. 总被引:4,自引:0,他引:4
OBJECTIVES: The morphological phenotype of endothelial cells (EC) is specific for individual types of vessels. There are, however, no studies on the phenotypical diversity of EC in human lung tissue. The influences exerted by physiological factors (e.g. age, sex) or pathological factors (e.g. pulmonary hypertension) on EC have not been ascertained up to now. METHODS: In order to determine the influence of pulmonary hypertension (PH), age and sex on EC, we localized the expression of the endothelial marker CD34 immunohistologically by light microscopy and laser scanning microscopy in lung tissue specimens from children and adults. RESULTS: Capillary EC showed a stronger staining reaction than EC in arteries, veins, arterioles or venules. The staining intensity increased with age in veins and arteries and decreased with age in venules, arterioles and capillaries. Sex exerted no statistically significant influence. CD34 was generally more strongly expressed in specimens with PH than in those without. CONCLUSION: The study demonstrates for the first time that (1) CD34 is heterogeneously expressed by human pulmonary EC, and (2) the physiological/pathophysiological factors age/PH influence CD34 expression. Hence a correlation between CD34 expression and its role as adhesion molecule and a link between CD34 expression and maturation are subject of discussion. 相似文献
52.
Simon F Johnen G Krismann M Müller KM 《Virchows Archiv : an international journal of pathology》2005,447(4):762-767
In a case of a 67-year-old man with two different early stages of a predominantly epithelioid mesothelioma (“mesothelioma
in situ”, “early-stage mesothelioma”), chromosomal imbalances were determined by comparative genomic hybridisation (CGH),
a molecular cytogenetic technique to detect chromosomal gains and losses in tumour cells. In the case of the mesothelioma
in situ cells, nine different chromosomal alterations could be detected (losses on 3p, 5q, 6q, 8p, 9p, 15q, 22q, Y; gain on
7q), whereas the early-stage mesothelioma showed the same defects except for the gain on 7q. The simultaneous losses of 6q,
9p and 22q, as well as other chromosomal regions, correlate well with the most common defects previously found in 90 cases
of more-advanced-stage mesotheliomas using CGH. These data demonstrate that initial chromosomal defects in early stages of
mesotheliomas can be detected by conventional CGH in combination with laser microdissection. The molecular cytogenetic findings
support the histological diagnosis of a pleural mesothelioma. The surprisingly high number and extent of genomic alterations
found in the examined case probably reflects the genomic instability in the tumour cells and indicates a “genetic chaos” even
in earlier stages of malignant mesotheliomas. 相似文献
53.
C. Kuhnen Edina Tolnay Hans Ulrich Steinau Bruno Voss Klaus-Michael Müller 《Virchows Archiv : an international journal of pathology》1998,432(4):337-342
Overexpression of c-Met receptor/hepatocyte growth factor (scatter factor) system (c-Met/HGF/SF) as a physiologically paracrine
cellular signaling system is thought to be involved in the progression of malignant tumours. In 26 synovial sarcomas and epithelioid
sarcomas, c-Met and HGF/SF expression was analysed immunohistochemically. There were 10 biphasic synovial sarcomas, 7 of which
showed moderate to strong c-Met expression in epithelial areas compared with the fibrous component, with corresponding expression
of HGF/SF. Six of 9 monophasic fibrous synovial sarcomas showed only very faint c-Met and corresponding HGF/SF expression.
In 7 epithelioid sarcomas strong expression of c-Met and HGF/SF was observed within epithelioid tumour cells. Non-radioactive
in situ hybridization demonstrated the synthesis of c-Met receptor in tumor cells by detecting c-met-mRNA. This analysis shows
that in synovial sarcomas and epithelioid sarcomas, tumour entities with epithelial and mesenchymal structures, c-Met and
HGF/SF overexpression can be detected, indicating a role of this signaling system in these subtypes of sarcoma, and especially
in the more epithelioid tumour phenotype. An autocrine interaction between overexpressed c-Met receptor and HGF/SF may be
hypothesized.
Received: 21 July 1997 / Accepted: 19 November 1997 相似文献
54.
Suicide gene therapy for pediatric tumors 总被引:2,自引:0,他引:2
Beltinger C Uckert W Debatin KM 《Journal of molecular medicine (Berlin, Germany)》2001,78(11):598-612
Tumor gene therapy is potentially very specific and efficacious. Suicide genes are promising tools in the arsenal of tumor gene therapy. However, problems of tumor targeting, low in vivo efficacy of nucleic acid transfer, and recent reports of adverse effects hinder the translation of this approach into clinical practice. Therefore vector design, tumor targeting, mechanisms of cell kill and killing of untransfected tumor cells must be improved. Once these problems are solved in vitro and in animal models, gene therapy holds great promise for pediatric oncology given the abundance of specific targets in pediatric tumors. This review describes the current state of preclinical research in tumor suicide gene therapy, provides an outline of pediatric suicide gene therapy protocols, and identifies potential targets in pediatric malignancies. 相似文献
55.
Simone Fulda Marek Los Claudia Friesen Klaus-Michael Debatin 《International journal of cancer. Journal international du cancer》1998,76(1):105-114
We have identified the CD95 system as a key mediator of chemotherapy-induced apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity of various solid tumor cell lines for drug-induced cell death corresponds to activation of the CD95 system. Upon drug treatment, strong induction of CD95 ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not in tumor cells which responded poorly to drug treatment (breast carcinoma and renal cell carcinoma). Blockade of CD95 using F(ab′)2 anti-CD95 antibody fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment induced CD95 expression, thereby increasing sensitivity for CD95-induced apoptosis. Drug-induced apoptosis critically depended on activation of caspases (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD-fmk strongly reduced drug-mediated apoptosis. The prototype substrate of caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment, suggesting that CD95-L triggered autocrine/paracrine death via activation of caspases. Our data suggest that chemosensitivity of solid tumor cells depends on intact apoptosis pathways involving activation of the CD95 system and processing of caspases. Our findings may have important implications for new treatment approaches to increase sensitivity and to overcome resistance of solid tumors. Int. J. Cancer 76:105–114, 1998.© 1998 Wiley-Liss, Inc. 相似文献
56.
Christian Denzel Franz Fellner Ralf Wutke Klaus Bazler Klaus-Michael Müller Werner Lang 《European Journal of Ultrasound》2003,16(3):161-167
OBJECTIVES: The aim of this study was to investigate whether ultrasonography can characterise plaque morphology and surfaces independent of the observer. METHODS: Computer-assisted image analysis of the grey scales of B-mode scans from 15 patients with stenoses of the internal carotid artery was performed and compared with the histopathological reports. In vitro angioscopy, was used to visualise the plaque surfaces of the thromboendarterectomy specimens. RESULT: Assessment of the internal plaque structure by ultrasound showed close agreement between the two observers (P<0.01) without correlation with the histopathological results. Ultrasonography was able to characterise the plaque surfaces in 93% of cases. CONCLUSION: This investigation showed that standardised computer-assisted analysis of the internal plaque structure correlates less closely than histological investigation, but agrees closely with the surface structure of the plaque. The exclusive use of digital image processing and standardisation of the investigative technique are expected to provide even better results. 相似文献
57.
58.
59.
Gold SM Schulz KH Hartmann S Mladek M Lang UE Hellweg R Reer R Braumann KM Heesen C 《Journal of neuroimmunology》2003,138(1-2):99-105
Neurotrophins like brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are thought to play an important role in neuronal repair and plasticity. Recent experimental evidence suggests neuroprotective effects of these proteins in multiple sclerosis (MS). We investigated the response of serum NGF and BDNF concentrations to standardized acute exercise in MS patients and controls. Basal NGF levels were significantly elevated in MS. Thirty minutes of moderate exercise significantly induced BDNF production in MS patients and controls, but no differential effects were seen. We conclude that moderate exercise can be used to induce neutrophin production in humans. This may mediate beneficial effects of physical exercise in MS reported recently. 相似文献
60.
Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells 总被引:2,自引:1,他引:1
Friesen C Lubatschofski A Kotzerke J Buchmann I Reske SN Debatin KM 《European journal of nuclear medicine and molecular imaging》2003,30(9):1262-1261
Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-xL, a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. 相似文献