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H. Krauss H. Hamperi v. Campenhausen H. Kalk Franke Frenzel Denecke L. Heilmeyer Hoepke Vaubel K. Lang G. Schubert H. Jahrmärker G. Schimert Emmrich Beckmann Heni Oberdisse R. Zenker Schrank Nase Rüd Werner Schulze A. Meesmann 《Journal of molecular medicine (Berlin, Germany)》1953,31(7-8):182-189
Ohne Zusammenfassung 相似文献
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Rachael Vaubel Valentina Zschernack Quynh T. Tran Sarah Jenkins Alissa Caron Dragana Milosevic James Smadbeck George Vasmatzis Daniela Kandels Astrid Gnekow Christof Kramm Robert Jenkins Benjamin R. Kipp Fausto J. Rodriguez Brent A. Orr Torsten Pietsch Caterina Giannini 《Brain pathology (Zurich, Switzerland)》2021,31(1):20-32
Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n = 53, 79%) or anaplastic PXA (A‐PXA, n = 14, 21%), including copy number analysis (ThermoFisher Oncoscan, n = 67), methylation profiling (Illumina EPIC array, n = 43) and targeted next generation sequencing (n = 32). The most frequent alterations were CDKN2A/B deletion (n = 63; 94%) and BRAF p.V600E (n = 51, 76.1%). In 7 BRAF p.V600 wild‐type cases, alternative driver alterations were identified involving BRAF, RAF1 and NF1. Downstream phosphorylation of ERK kinase was uniformly present. Additional pathogenic alterations were rare, with TERT, ATRX and TP53 mutations identified in a small number of tumors, predominantly A‐PXA. Methylation‐based classification of 46 cases utilizing a comprehensive reference tumor allowed assignment to the PXA methylation class in 40 cases. A minority grouped with the methylation classes of ganglioglioma or pilocytic astrocytoma (n = 2), anaplastic pilocytic astrocytoma (n = 2) or control tissues (n = 2). In 9 cases, tissue was available from matched primary and recurrent tumors, including 8 with anaplastic transformation. At recurrence, two tumors acquired TERT promoter mutations and the majority demonstrated additional non‐recurrent copy number alterations. Methylation class was preserved at recurrence. For 62 patients (92.5%), clinical follow‐up data were available (median follow‐up, 5.4 years). Overall survival was significantly different between PXA and A‐PXA (5‐year OS 80.8% vs. 47.6%; P = 0.0009) but not progression‐free survival (5‐year PFS 59.9% vs. 39.8%; P = 0.05). WHO grade remained a strong predictor of overall survival when limited to 38 cases defined as PXA by methylation‐based classification. Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation‐based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well‐defined morphology. 相似文献
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L. Zimmer J. Vaubel Prof. Dr. D. Schadendorf 《Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete》2012,63(12):952-960
Even early clinical studies showed that adjuvant chemotherapy achieved no therapeutic benefit for melanomas so that in the current guidelines its use is only recommended within the framework of clinical studies. For over 30 years interferons have been used in the adjuvant treatment of primary high risk melanomas as well as in the treatment of metastasized melanomas. They function in an antiviral, immune modulating and antitumor fashion. Direct and indirect effects on tumor cells could be demonstrated for interferons. In Europe low dosage interferon therapy is approved and has become widely established for stage II melanomas, whereas in the USA high dosage therapy for stage III and since March 2011 therapy with pegylated interferon in stage III are also approved. In this article the most important study results will be dealt with in detail. In summary, according to the current study situation therapy with interferon should be offered especially to patients with ulcerated primary melanoma and microscopic lymph node infiltration. Many attempts have been made in the last decades to positively influence the survival time of distant metastasized melanoma by systemic therapy. The recent development of the antibody ipilimumab against cytotoxic T-lymphocyte protein 4 (CTLA-4) could show for the first time a survival advantage in the therapy of melanoma patients in advance stage disease. The licensing of ipilimumab has meant that there is now a new standard available for the second line therapy of malignant melanoma which will be included in the guidelines on therapy of malignant melanoma. A further interesting option for adjuvant therapy is currently vaccination with the recombinant melanoma-associated protein 3 (MAGE-A3) protein in combination with the adjuvant AS015. 相似文献
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The compensatory increase in young Long-Evans rats was depressed by the ingestion of sodium nitrite administered at a dietary concentration of 10,000 and 25,000 ppm for a period of 21 days. The inhibition in compensatory ovarian response due to sodium nitrite was also reflected in reduced uterine weight gain. Body weights at necrospy were significantly reduced, indicating an inhibitory influence of sodium nitrite on growth. 相似文献
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Amy A. Swanson Caterina Giannini Andrew L. Folpe Daniel L. Van Dyke Kimberly K. Amrami William A. Michalak Rachael A. Vaubel 《Neuropathology》2018,38(3):309-314
We report a case of low‐grade fibromyxoid sarcoma arising within the median nerve. A 31‐year‐old woman presented with symptoms of carpal tunnel syndrome and an enlarging mass in her right palm over 1 year. MRI demonstrated a mass associated with the right median nerve with solid and cystic components. At surgery, the mass was located within the epineurium, could be bluntly dissected from the nerve fascicles, and was suspected to be a schwannoma. A 3.4 cm, tan‐pink, glistening, smooth, homogenous mass was submitted to pathology. Microscopically, the tumor was a solid and cystic circumscribed nodule with a dense fibrous pseudocapsule. The tumor cells were uniformly bland and spindle‐shaped, with small, hyperchromatic oval nuclei and were embedded in an alternating fibrous and myxoid stroma with a prominent curvilinear vasculature and perivascular sclerosis. The differential diagnosis for this lesion included myxoid neurofibroma, schwannoma, soft tissue perineurioma, low‐grade malignant peripheral nerve sheath tumor and low‐grade fibromyxoid sarcoma. The tumor cells expressed MUC4, GLUT‐1, and vimentin and were negative for S‐100 protein, epithelial membrane antigen, smooth muscle actin, desmin, claudin‐1, neurofilament and SOX10. Fluorescence in situ hybridization, with a break‐apart probe strategy, demonstrated FUS rearrangement, consistent in this morphological context with the low‐grade fibromyxoid sarcoma‐associated FUS‐CREB3L2 or FUS‐CREB3L1 fusions. Low‐grade fibromyxoid sarcoma is exceptionally rare in the peripheral nerve, with only a single previously reported case. Nonetheless, as our case illustrates, this entity must be included in the differential diagnosis of unusual intraneural mesenchymal tumors. As in all other locations, intraneural low‐grade fibromyxoid sarcomas should be excised with negative margins. Patients with this disease require long‐term clinical follow‐up, given this tumor's propensity for very late distant metastases to the lungs and other sites. 相似文献