全文获取类型
收费全文 | 260篇 |
免费 | 20篇 |
专业分类
儿科学 | 4篇 |
基础医学 | 60篇 |
临床医学 | 4篇 |
内科学 | 6篇 |
神经病学 | 113篇 |
特种医学 | 8篇 |
外科学 | 9篇 |
肿瘤学 | 76篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 6篇 |
2013年 | 7篇 |
2012年 | 2篇 |
2011年 | 4篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 6篇 |
2007年 | 8篇 |
2006年 | 7篇 |
2005年 | 9篇 |
2004年 | 14篇 |
2003年 | 12篇 |
2002年 | 20篇 |
2001年 | 18篇 |
2000年 | 14篇 |
1999年 | 22篇 |
1998年 | 8篇 |
1997年 | 12篇 |
1996年 | 11篇 |
1995年 | 12篇 |
1994年 | 7篇 |
1993年 | 10篇 |
1992年 | 14篇 |
1991年 | 12篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
排序方式: 共有280条查询结果,搜索用时 15 毫秒
11.
12.
Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline 总被引:11,自引:0,他引:11
Thal DR Ghebremedhin E Orantes M Wiestler OD 《Journal of neuropathology and experimental neurology》2003,62(12):1287-1301
Sporadic, late-onset Alzheimer disease (AD) constitutes the most frequent cause of dementia in the elderly population. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis/lipohyalinosis (AS/LH). The present study was carried out to examine the coincidence of these small vessel pathologies during the development of cognitive deficits, amyloid beta-protein (A beta) deposition, and neurofibrillary tangle (NFT) formation in sporadic late-onset AD. We correlated the clinical dementia rating (CDR) score, the sequential extension of AD-related A beta deposition into different parts of the brain, and the extension of NFTs to involve more brain regions with the distribution of CAA and AS/LH in 52 human autopsy brains. The extension of CAA and AS/LH to involve different areas of the brain was associated with a rise of CDR scores and an increase in the extension of A beta deposition and NFT generation. AD cases showed a higher number of regions with CAA and AS/LH compared to nondemented patients with AD-related pathology and controls. Moreover, we demonstrated a hierarchical sequence in which the different regions of the brain exhibited CAA and AS/LH-affected vessels, allowing the distinction of 3 stages in the development of CAA and AS/LH. The first stage of CAA involved leptomeningeal and neocortical vessels. The second stage was characterized by additional A beta deposition in allocortical and midbrain vessels. Finally, in a third stage, CAA was observed in the basal ganglia, the thalamus, and in the lower brainstem. In contrast, AS/LH initially affected the basal ganglia in stage A. In stage B this pathology made inroads into the deep white matter, the leptomeningeal arteries of the cortex, the cerebellum, and into the thalamus. Stage C was characterized by AS/LH in brainstem vessels. Our results demonstrate widespread CAA and AS/LH to be associated with the development of cognitive deficits in AD. A combination of both CAA and AS/LH may, therefore, contribute to neurodegeneration in AD. These data also suggest that small vessel disease due to arteriosclerosis and fibrolipohyalinosis is a potential target for the treatment of AD. 相似文献
13.
Urbach H Scheffler B Heinrichsmeier T von Oertzen J Kral T Wellmer J Schramm J Wiestler OD Blümcke I 《Epilepsia》2002,43(1):33-40
BACKGROUND AND PURPOSE: Focal cortical dysplasia of Taylor's balloon-cell type (FCD-BC) are a frequent cause of pharmacoresistant epilepsy in young patients. In order to characterize FCD-BC, we coupled MRI and histopathology, and analyzed the clinical outcome following epilepsy surgery. METHODS: From an epilepsy data bank with 547 histological specimens, 17 FCD-BC were re-evaluated of which high resolution MRI was available. Five additional FCD-BC were prospectively identified by MRI. Histopathological and immunohistochemical features were related to MRI. Outcome following lesionectomy was analyzed as determined on routine examinations 3, 6 and 12 months following surgery. RESULTS: All but one lesion were located outside the temporal lobe. A markedly hyperintense funnel-shaped subcortical zone tapering towards the lateral ventricle was the characteristic finding on FLAIR MRI. Histopathologically, the subcortical zone of the FCD-BC displayed hypomyelinated white matter with radially oriented balloon cells and gliosis. Dysplastic neurons were found in the adjacent, disorganized cortex. All patients with complete lesionectomy were seizure free one year following surgery. CONCLUSION: Focal cortical dysplasias of Taylor's balloon-cell type (FCD-BC) have characteristic MRI and histopathological findings. MRI recognition is important, since outcome following resective surgery is favorable. 相似文献
14.
Wolfgang Hartmann Boris Digon-S?ntgerath Arend Koch Anke Waha Elmar Endl Indra Dani Dorota Denkhaus Cynthia G Goodyer Niels S?rensen Otmar D Wiestler Torsten Pietsch 《Clinical cancer research》2006,12(10):3019-3027
PURPOSE: Medulloblastomas represent the most frequent malignant brain tumors of childhood. They are supposed to originate from cerebellar neural precursor cells. Recently, it has been shown that Sonic Hedgehog-induced formation of medulloblastoma in an animal model is significantly enhanced by activation of the phosphatidylinositol 3'-kinase (PI3K) signaling pathway. EXPERIMENTAL DESIGN: To examine a role for PI3K/AKT signaling in the molecular pathogenesis of human medulloblastoma, we did an immunohistochemical study of the expression of Ser473-phosphorylated (p)-AKT protein in 22 medulloblastoma samples: All samples displayed p-AKT expression. To investigate if an activated PI3K/AKT pathway is required for medulloblastoma cell growth, we treated five human medulloblastoma cell lines with increasing concentrations of the PI3K inhibitor LY294002 and analyzed cellular proliferation and apoptosis. The antiproliferative effect could be antagonized by overexpressing constitutively active AKT. As the activation of PI3K/AKT signaling may be associated with alterations of the PTEN gene located at 10q23.3, a chromosomal region subject to frequent allelic losses in medulloblastoma, we screened PTEN for mutations and mRNA expression. RESULTS: Proliferation of all of the medulloblastoma cell lines was dependent on PI3K/AKT signaling, whereas apoptosis was not prominently affected. Allelic loss was detected in 16% of the cases. One medulloblastoma cell line was found to carry a truncating mutation in the PTEN coding sequence. Even more important, PTEN mRNA and protein levels were found to be significantly lower in medulloblastomas compared with normal cerebellar tissue of different developmental stages. Reduction of PTEN expression was found to be associated with PTEN promoter hypermethylation in 50% of the tumor samples. CONCLUSIONS: We conclude that activation of the PI3K/AKT pathway constitutes an important step in the molecular pathogenesis of medulloblastoma and that dysregulation of PTEN may play a significant role in this context. 相似文献
15.
Calaminus G Bamberg M Harms D Jürgens H Kortmann RD Sörensen N Wiestler OD Göbel U 《Neuropediatrics》2005,36(2):71-77
PURPOSE: The aim of the present study was to evaluate survival and factors influencing long-term outcome of patients with AFP/beta-HCG secreting (non-seminomatous) central nervous system germ cell tumors (secCNSGCT), who were prospectively collected in the cooperative MAKEI (German: maligne Keimzelltumoren) 89 protocol. PATIENTS AND METHODS: Between January 1989 and January 1994, 28 patients with secCNS GCT were registered and treated according to the MAKEI 89 protocol. The protocol recommended, after a clinically or histologically proven diagnosis and cisplatin-based chemotherapy, a resection of residual tumor and craniospinal irradiation (30 Gy) with a tumor boost (20 Gy). RESULTS: The estimated (Kaplan-Meier) event-free survival (EFS) of protocol patients is 0.57 +/- 0.09 (n = 28) and the relapse-free survival (RFS) is 0.67 +/- 0.10 (at five and ten years). With respect to long-term survival, the combination of marked neurological symptoms at diagnosis along with primary tumor resection seem to be the main negative prognostic risk factors (Fisher exact test p < 0.05). CNS dissemination at diagnosis can also be considered as a negative risk factor as 3 of 5 patients with primary dissemination died of the disease. CONCLUSION: Cisplatin-based three agent chemotherapy followed by resection of the residual tumor and craniospinal irradiation (CSI) with tumor boost is a successful and well-tolerated treatment for secCNSGCTs. The possibility of a clinical diagnosis based on MRI and tumor markers together with the use of modern neurosurgical techniques gives us the chance to postpone or even avoid major surgery. This gives an additional chance to reduce acute morbidity and further decrease late effects. 相似文献
16.
Montesinos-Rongen M Besleaga R Heinsohn S Siebert R Kabisch H Wiestler OD Deckert M 《Virchows Archiv : an international journal of pathology》2004,444(5):436-438
Simian virus 40 (SV40) is known to induce primary brain tumors and lymphomas in animal models. Recently, it was also associated with the pathogenesis of human non-Hodgkins lymphomas. In the present study, we investigated primary central nervous system lymphomas (PCNSL), a defined subgroup of diffuse large B-cell lymphoma confined to the central nervous system, for the presence of SV40 DNA. Frozen tissue samples of 23 PCNSL derived from human immunodeficiency virus-negative patients were analyzed by two different, fully nested polymerase chain reaction protocols. SV40 DNA sequences could not be detected in any of these samples. Thus, SV40 can be added to the list of viruses that have already been excluded as pathogenetically relevant cofactors in PCNSL. 相似文献
17.
18.
Steffel J Wernig M Knauf U Kumar S Wiestler OD Wernig A Brüstle O 《Stem cells (Dayton, Ohio)》2003,21(2):181-189
There is increasing evidence that muscle-derived precursor cells can, under appropriate conditions, give rise to other than myogenic cell types. Transplantation into the embryonic ventricular zone provides a unique opportunity to study the migration and differentiation of non-neural somatic progenitor cells in response to instructive cues within the developing neuroepithelium. Here, we demonstrate that myogenic cell lines grafted into the ventricles of rat embryos showed widespread migration into several host brain compartments. In contrast to incorporation patterns observed after transplantation of neural cells, grafted myoblasts incorporated virtually exclusively along endogenous blood vessels. Preferential incorporation sites included cortex, olfactory bulb, hippocampus, striatum, thalamus, hypothalamus, and tectum. While the engrafted myoblasts showed no evidence of neural differentiation, a fraction exhibited pronounced coexpression of endothelial marker antigens. These findings support the concept of a close developmental relationship between the myogenic and the endothelial lineages. Used as a delivery system, transfected myoblasts may be exploited for widespread gene transfer to the perivascular compartment of the perinatal central nervous system. 相似文献
19.
Ependymome entstehen aus den
wandauskleidenden Ependymzellen der Ventrikel einschließlich des
Zentralkanals des Rückenmarks. Entsprechend können sie
ventrikelnah im Bereich des Gehirns sowie im Inneren des
Rückenmarks und an dessen Ende, dem Filum terminale, beobachtet
werden. Sie stellen ca. 3–9% aller neuroepithelialen
Tumoren,wobei der Anteil im Kindesalter deutlich höher ist—hier
machen sie bis zu 20% aller soliden intrakraniellen Tumoren aus.
In dem vorliegenden Text sollen die intrakraniellen Ependymome
behandelt werden—auf die spinalen Ependymome, die in der Regel
als intramedulläre Tumoren auftreten, soll aufgrund der
grundsätzlichen Verschiedenheiten spinaler und intrakranieller
Tumoren hier nicht eingegangen werden. Die intrakraniellen
Manifestationen der Ependymome führen zu Anfällen oder zu
neurologischen Ausfallserscheinungen. Je nach Lage des Tumors,
insbesondere bei Lokalisation des Tumors in der hinteren
Schädelgrube tritt häufig ein begleitender Hydrozephalus auf.
Die Therapie der Wahl ist die mikrochirurgische Exstirpation,
die auf eine maximale Entfernung des Tumors abzielt. Rezidive
entstehen in der Regel lokal, selten auch als Aussaat über den
Liquorraum. Aufgrund der Rezidivneigung ist eine regelmäßige
Nachsorge unerlässlich. 相似文献
20.
Jung G Brandl M Eisner W Fraunberger P Reifenberger G Schlegel U Wiestler OD Reulen HJ Wilmanns W 《International journal of cancer. Journal international du cancer》2001,91(2):225-230
After adoptive transfer of pre-activated lymphocytes into the operation cavity of glioma patients, tumor regression and improved survival have been reported in some patients. Results were most impressive when bispecific antibodies with tumor x CD3 specificity were also applied. In this study, we attempted to avoid time-consuming pre-activation procedures for adoptively transferred cells by using a combination of bispecific antibodies directed to the EGF receptor (EGFR) on tumor cells and to CD3 and CD28 on T cells. Eleven patients with high-grade malignant glioma received 3 injections of 2 bispecific antibody fragments (EGFR x CD3 and EGFR x CD28) together with freshly isolated autologous lymphocytes via an Ommaya reservoir. Intracavitary fluid aspirated during immunotherapy was examined for markers of T-cell activation. Increased levels of soluble IL-2 receptor and TNF-alpha were detected in the intracavitary fluid of all patients tested. Two of the 11 treated patients experienced a beneficial response to therapy as defined by a transient contrast enhancement in subsequent MRI scans and prolonged survival. Side effects were transient and consisted of fever, nausea, headache and aggravation of pre-existing neurologic deficits. These adverse effects were most likely due to the antibody construct containing anti-CD3 specificity. Two patients developed cerebral edema and required steroid treatment. 相似文献