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排序方式: 共有198条查询结果,搜索用时 15 毫秒
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PURPOSE: To study adhesion, penetration and internalization of BCG and effector-cells to and into three-dimensional in vitro cell aggregates from benign and malignant urothelial origin mimicking small in vitro tumors. MATERIALS AND METHODS: Multicellular spheroids (MCS) were generated by "liquid-overlay" technique. Adhesion and penetration of viable FITC-labelled BCG into MCS from urothelial cancer cell lines and normal urothelial cells was studied by electron microscopy (TEM) and fluorescence microscopy. Spheroid growth during BCG-co-incubation was determined by light microscopy. Peripheral blood mononuclear cells (PBMC) were stimulated with BCG to generate BCG-activated-killer (BAK) cells. The infiltration of these effectors and of lymphokine-activated killer (LAK) cells into MCS was examined at different intervals by means of immunohistochemistry. The resulting cytotoxicity was judged in a 3H-l-methionine release assay. RESULTS: BCG adhered to MCS from tumor cells but not to benign cell MCS. Intracellular internalization of the bacteria was detectable in superficial tumor cell-layers (1-5) whereas BCG was not found in deeper layers. Proliferation of malignant MCS was reduced in the presence of BCG. Benign MCS showed contact inhibition growth arrest, which was not altered by BCG. BAK and LAK effector cells both infiltrated tumor cell MCS as opposed to unstimulated PBMC. In contrast to LAK cells, BAK cells did not infiltrate into benign cell MCS and were not cytotoxic towards them. CONCLUSION: With regard to the clinical situation the selective adhesion and internalization of BCG to malignant cells might explain why BCG has been rarely found in follow-up biopsies in tumor free patients. More interestingly, the selective adhesion of BCG to and infiltration of BAK effector cells into malignant cell spheroids suggests a selective mode of action of BCG. 相似文献
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Alexander Hackel Aleksandra Aksamit Kirsten Bruderek Stephan Lang Sven Brandau 《European journal of immunology》2021,51(2):319-330
During inflammatory processes, tissue environmental cues are influencing the immunoregulatory properties of tissue-resident mesenchymal stem/stromal cells (MSC). In this study, we elucidated one of the molecular and cellular responses of human MSC exposed to combinations of inflammatory cytokines. We showed that during multi-cytokine priming by TNF-α, IL-1β, and IFN-γ, IL-1β further augmented the well-established immunoregulatory activity induced by TNF-α/IFN-γ. On the molecular level, TNF-α and IL-1β enhanced the expression of IFN-γ receptor (IFN-γR) via NF 'kappa-light-chain-enhancer' of activated B-cells (NF-κΒ) signaling. In turn, enhanced responsiveness to IFN-γ stimulation activated STAT5 and p38-MAPK signaling. This molecular feedback resulted in an increased IL-8 release and augmented recruitment of polymorphonuclear granulocytes (PMN). Our study suggests the possibility that responses of MSC to multi-cytokine priming regimens may be exploited therapeutically to fine-tune inflammatory activity in tissues. This study elucidates molecular mechanisms underlying the immunological priming of mesenchymal stromal cells (MSC) and their interaction with neutrophils. 相似文献
4.
The clinical entity of multicentric cancerisation comprises multiple carcinomas arising from different anatomical sites and widespread carcinomas of multicentric origin. Over a period of 12 years multicentric cancerisation was diagnosed in 42 out of 150 patients (28%) with primary tumours of the oral cavity or the oropharynx. Patients with multicentric cancerisation are younger at the time of diagnosis of their first primary tumour, and their survival rates are worse compared with patients with only primary tumour. We conclude from our results that a routine panendoscopy should be performed in every patient presenting with a carcinoma of the oral cavity or the oropharynx to rule out a synchronous second primary tumour. Furthermore, these patients should be encouraged to stop smoking, to stop drinking spirits and to undergo regular follow-up examination. 相似文献
5.
Brandau T 《International journal of pharmaceutics》2002,242(1-2):179-184
Since the handling of many active agents in its pure form has many problems, microencapsulation is used to have better properties in the product. With the patented BRACE-Processes it is possible to encapsulate a very wide range of materials in monodisperse Microspheres or Microcapsules in a diameter range of 50-6000 microm with a very narrow size distribution. The Microsphere Units from BRACE can be customer tailored to the materials and all necessary specifications as FDA, GMP/GLP, EX, CIP, WIP etc. The throughput of the BRACE Microsphere Units ranges between 10 ml per h (small laboratory scale) up to over 1000 l per h (production scale) while the production cost are very low, especially if compared directly to competitive processes as spray-drying or fluidized bed coating. 相似文献
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Panaretto KS Lee HM Mitchell MR Larkins SL Manessis V Buettner PG Watson D 《The Medical journal of Australia》2005,182(10):514-519
OBJECTIVES: To evaluate the impact of a community-based, collaborative, shared antenatal care intervention (the Mums and Babies program) for Indigenous women in Townsville. DESIGN AND PARTICIPANTS: Prospective cohort study of women attending Townsville Aboriginal and Islander Health Service (TAIHS) for shared antenatal care with a singleton Indigenous birth between 1 January 2000 and 31 December 2003 (456 women; the MB group), compared with a historical control group of 84 women who attended TAIHS for antenatal care before the intervention between 1 January 1998 and 30 June1999, and a contemporary control group of 540 women who had a singleton birth at Townsville Hospital between 1 January 2000 and 30 June 2003, but did not attend TAIHS for antenatal care. INTERVENTION: Integration of previously autonomous service providers delivering shared antenatal care from TAIHS. MAIN OUTCOME MEASURES: Patterns of antenatal visits, proportion of women undertaking key antenatal screening, and perinatal outcomes. RESULTS: The number of Indigenous women who entered the MB program and gave birth at Townsville Hospital rose from 23.8% in 2000 to 61.2% in 2003. The number of antenatal care visits per pregnancy increased from three (interquartile [IQ] range, 2-6) in the historical control group to seven (IQ range, 4-10) in the MB group (P < 0.001). 88% of women in the MB group had at least one ultrasound. About 90% of all women attending for antenatal care were screened for sexually transmitted infections. In the MB group, there was a significant reduction in preterm births compared with the contemporary control group (8.7% v 14.3%, P < 0.01). There was no significant reduction in the prevalence of low birthweight births or perinatal mortality. CONCLUSION: A community-based collaborative approach to shared antenatal care services increased access to antenatal care and was associated with fewer preterm births among Indigenous women in Townsville. The model may be adaptable in other urban centres with multiple antenatal care providers and significant numbers of Indigenous people across Australia. 相似文献
9.
Immunotherapy of experimental bladder cancer with recombinant BCG expressing interferon-gamma 总被引:9,自引:0,他引:9
Arnold J de Boer EC O'Donnell MA Böhle A Brandau S 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2004,27(2):116-123
One of the most potent immunotherapies presently used is the application of Bacillus Calmette Guérin (BCG) to prevent recurrences of superficial bladder cancer. Despite its successful use, nonresponders and certain side effects remain a major obstacle. Therefore, current studies aim at developing recombinant BCG (rBCG) strains to further improve the effectiveness of the therapy. In BCG-treated patients a strong local induction of Th1-like cytokines was observed. For this reason rBCG-strains secreting Th1-like cytokines might be potentially useful agents to improve this type of immunotherapy. Because we previously demonstrated the essential role of IFNgamma in BCG-induced antitumor responses, in this study a rBCG strain secreting murine IFNgamma (rBCG-IFNgamma) was generated and tested for its immunostimulatory capacity in several in vitro and in vivo test systems. In vitro rBCG-IFNgamma specifically up-regulated expression of MHC class I molecules on a murine bladder cancer cell line (MB49), compared to the rBCG control strain (transfected with an empty vector). In a murine model of experimental bladder cancer, intravesical instillation of rBCG-IFNgamma resulted in an enhanced recruitment of CD4+ T-cells into the bladder and further induced the local expression of IL-2 and IL-4 cytokines (mRNA) compared to control rBCG. With a low-dose treatment regimen for murine orthotopic bladder cancer, rBCG-IFNgamma significantly prolonged survival, whereas the therapeutic effect of wild-type control BCG did not reach statistical significance. We conclude that this recombinant BCG strain has enhanced immunostimulatory potential and might offer new opportunities in the treatment of bladder cancer. 相似文献
10.
Arblaster G Streather C Hugill L McKenzie M Missenden J 《Nursing standard (Royal College of Nursing (Great Britain) : 1987)》2004,18(43):33-37
Healthcare support workers (HCSWs) are at the front line of patient care delivery. It is essential that they are appropriately trained and competent in the skills required to deliver the fundamentals of care. There is also a need for HCSWs to have access to continuing professional development that offers a career pathway. The University Hospitals Coventry and Warwickshire NHS Trust has developed a framework for career progression that incorporates three phases of continuing professional development. These are organised and co-ordinated by a dedicated support worker training team comprising four registered nurses plus senior support workers in the role of peripatetic NVQ Care assessors. 相似文献