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81.
c-myc and N-myc belong to the myc family of proteins that plays an important role in cell proliferation, differentiation and apoptosis. The N-myc gene is amplified in aggressive neuroblastoma and c-myc is overexpressed in many lymphomas and cancers. However, c-myc has not been implied in tumorigenesis or progression of neuroblastoma. We therefore investigated the so far unknown effects of c-myc overexpression on the aggressiveness of neuroblastoma cells with single copy N-myc. c-myc overexpression in serum-deprived murine NXS2 neuroblastoma cells led to cell cycle progression and massive apoptosis, causing a net decrease of viable cells. In serum-replete medium c-myc caused NXS2 cells to arrest in G2/M. Furthermore, c-myc decreased clonogenic growth of neuroblastoma cells. Taken together, these data suggest that c-myc attenuates the malignant phenotype of NXS2 neuroblastoma cells. Thus, although c-myc increased NXS2 tumor mass in vivo, c-myc appears to have decreased malignant potency in neuroblastoma cells compared to N-myc. This may be one reason why c-myc does not play a role in neuroblastomagenesis. 相似文献
82.
Krismann M Adams H Jaworska M Müller KM Johnen G 《Virchows Archiv : an international journal of pathology》2000,437(3):248-255
Solitary fibrous tumours (SFTs) of the pleura, in contrast to malignant mesothelioma, occur independently of previous asbestos
exposure. They are benign tumours, but may recur if the stalk to the adjacent pleural or lung tissue remains in situ during
surgical removal. The molecular pathology of SFTs is largely unknown. We used comparative genomic hybridisation (CGH) to characterise
12 localised SFTs and 12 predominantly sarcomatoid mesotheliomas. Fifty-eight percent of the investigated SFTs did not show
any chromosomal imbalances. The most frequent defects were losses on chromosome arms 13q (33%), 4q and 21q (17% each). Significant
gains were seen at chromosome 8 and at 15q in two cases each. There was no correlation between tumour size and molecular pathology
findings. In contrast, 75% of the mesotheliomas carried chromosomal defects. On average, the mesotheliomas showed over three
times as many defects per tumour as the SFTs. Localisation of several frequent losses and gains were similar to those of the
SFTs. Therefore, in individual cases, a clear distinction between SFTs and sarcomatoid mesotheliomas is not possible based
on CGH analysis alone. Further molecular characterisation of this rare tumour entity will be necessary to elucidate possible
genes involved in early tumorigenesis.
Received: 24 January 2000 / Accepted: 22 March 2000 相似文献
83.
Edina Tolnay Thorsten Wiethege Klaus-Michael Müller 《Virchows Archiv : an international journal of pathology》1997,430(3):209-212
Thrombomodulin (TM) is an endothelial surface glycoprotein that acts as a natural anticoagulant. It inhibits thrombin and accelerates the activation of the anticoagulant protein C. TM has been detected in dermal keratinocytes, where it is associated with terminal differentiation. It can also be detected in various types of squamous malignant neoplasms and in malignancies of endothelial and mesothelial origin, such as Kaposi's sarcoma or malignant mesothelioma, but is absent in pulmonary adenocarcinomas (AC). Seventy-two lung tumour specimens [33 squamous cell carcinomas (SQCC), 23 AC, 1 large cell carcinoma, 8 small cell lung cancers (SCLC) and 7 multidifferentiated tumours (MT)] were analysed immunohistochemically by staining with an anti-TM antibody in order to assess TM expression. All of the SQCC stained positively for TM. In contrast, only 9 AC and 4 MT and none of the SCLC showed positive anti-TM staining. Seven hyperplastic bronchial epithelial specimens and eight preneoplastic bronchial lesions (five cases of moderate dysplasia, two cases of severe dysplasia and one case of carcinoma in situ) were used as controls.Normal or hyperplastic areas of bronchial epithelium revealed no positive reaction. However, a distinct positive anti-TM staining pattern related to the degree of keratiniziation of dysplastic lesions was seen. The present results suggest that anti-TM immunostaining is a useful marker for squamous cell carcinoma in the differential diagnosis of pulmonary carcinoma, also indicating keratinocyte differentiation in dysplastic bronchial epithelium. 相似文献
84.
ATP citrate lyase (ACL) catalyzes the formation of cytosolic acetyl-CoA, which is mainly used for the biosynthesis of fatty
acids and sterols. In this paper, we show for the first time that in filamentous fungi two different subunits of ACL are encoded
by two separate genes. This is in contrast to animals where ACL is encoded by a single gene. Data are presented on acl genes from the filamentous fungi Sordaria macrospora and Gibberella pulicaris. In S. macrospora, both genes, acl1 and acl2, are clustered within a region of 10 kb and are divergently transcribed.
Received: 13 September / 2 November 1999 相似文献
85.
Irit Allon Ahmi Ben-Yehudah Raz Dekel Jan-Helge Solbakk Klaus-Michael Weltring Gil Siegal 《Medicine, health care, and philosophy》2017,20(1):3-11
Nanomedicine offers remarkable options for new therapeutic avenues. As methods in nanomedicine advance, ethical questions conjunctly arise. Nanomedicine is an exceptional niche in several aspects as it reflects risks and uncertainties not encountered in other areas of medical research or practice. Nanomedicine partially overlaps, partially interlocks and partially exceeds other medical disciplines. Some interpreters agree that advances in nanotechnology may pose varied ethical challenges, whilst others argue that these challenges are not new and that nanotechnology basically echoes recurrent bioethical dilemmas. The purpose of this article is to discuss some of the ethical issues related to nanomedicine and to reflect on the question whether nanomedicine generates ethical challenges of new and unique nature. Such a determination should have implications on regulatory processes and professional conducts and protocols in the future. 相似文献
86.
Claudia Friesen Mareike Roscher Inis Hormann Iduna Fichtner Andreas Alt Ralf A. Hilger Klaus-Michael Debatin Erich Miltner 《Oncotarget》2013,4(5):677-690
Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. 相似文献
87.
88.
Karin Oechsle Wiebke Jensen Tobias Schmidt R��diger Reer Klaus-Michael Braumann Maike de Wit Carsten Bokemeyer 《Supportive care in cancer》2011,19(5):613-619
Purpose
Quality of life is of major importance in patients with advanced cancers undergoing palliative chemotherapy. In contrast to the number of studies on physical activity in patients with curable malignancies, data on patients undergoing palliative chemotherapy are scarce. 相似文献89.
90.
Over the past decade, xenografting human leukemia cells into mice with different levels of immunodeficiency, with or without preconditioning, has provided an important tool to study various aspects of leukemia biology and to identify distinct clinical risk groups for evaluation of novel therapeutic strategies, as well as the possibility of amplifying human leukemia cells in vivo. Interestingly, these models using human acute lymphoblastic leukemia and acute myeloid leukemia cells as xenografts recapitulate many clinical features of the disease. Similar to the human environment (for example, in the bone marrow), transplanted leukemia cells in the murine setting are exposed to both favorable and unfavorable conditions for engraftment that may exert a distinct pressure for selection of subclones. Thus, results obtained in these models may vary depending on the experimental setup. The impact of in vivo growth of human leukemia cells on the background of a more or less hostile murine environment for leukemia biology and the course of the disease in patients are discussed in the context of the diversity of xenograft models. 相似文献