全文获取类型
收费全文 | 211篇 |
免费 | 28篇 |
学科分类
医药卫生 | 239篇 |
出版年
2023年 | 3篇 |
2022年 | 12篇 |
2021年 | 8篇 |
2020年 | 8篇 |
2019年 | 6篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 6篇 |
2015年 | 8篇 |
2014年 | 8篇 |
2013年 | 14篇 |
2012年 | 14篇 |
2011年 | 16篇 |
2010年 | 7篇 |
2009年 | 9篇 |
2008年 | 14篇 |
2007年 | 13篇 |
2006年 | 10篇 |
2005年 | 7篇 |
2004年 | 13篇 |
2003年 | 9篇 |
2002年 | 15篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1995年 | 1篇 |
1992年 | 6篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有239条查询结果,搜索用时 0 毫秒
1.
2.
3.
Expression of inhibitor-of-apoptosis protein family members in malignant mesothelioma 总被引:4,自引:0,他引:4
Inhibitor-of-apoptosis proteins (IAPs) mediate cancer cell survival and chemoresistance. We analyzed the expressions of X-linked IAP (XIAP), survivin, and livin in malignant mesothelioma. Ten effusions were analyzed for XIAP, survivin, and livin expression using immunoblotting. Based on the immunoblotting results, 112 mesotheliomas from 94 patients (pleural, n = 77; peritoneal, n = 35; solid, n = 68; effusions, n = 44) were immunostained for XIAP and survivin expression. Results were analyzed for associations with anatomic site (pleura versus peritoneum), specimen type (solid versus effusion), proliferation (Ki-67 score), and survival. Immunoblotting showed expression of XIAP in 9 of 10 effusions and that of survivin in 4 of 10 effusions, but no expression of livin. Immunohistochemistry showed cytoplasmic XIAP expression in 71 of the 112 (63%) tumors. XIAP expression was significantly higher in peritoneal mesotheliomas than in pleural mesotheliomas (P = .001) and in effusions than in solid lesions (P = .017). Cytoplasmic survivin was found in 75 of the 112 (67%) tumors and showed no site-related difference. Nuclear survivin was expressed in 37 of the 112 (33%) tumors, with a trend for positive association with the Ki-67 score (P = .051). Nuclear survivin (P = .003) and Ki-67 (P = .013) were downregulated in effusions as compared with solid tumors. Higher XIAP expression and Ki-67 score were associated with a trend for poor overall survival (P = .064 for both) in the univariate analysis. XIAP and survivin, but not livin, are frequently expressed in malignant mesotheliomas. Nuclear survivin expression is reduced in effusions as compared with solid lesions concomitantly with reduced proliferation. XIAP is upregulated in mesothelioma effusions and peritoneal mesotheliomas, suggesting a prosurvival role in malignant mesothelioma cells, particularly at these anatomic sites. 相似文献
4.
Bacali Cecilia Baldea Ioana Moldovan Marioara Carpa Rahela Olteanu Diana Elena Filip Gabriela Adriana Nastase Vivi Lascu Liana Badea Mandra Constantiniuc Mariana Badea Florin 《Clinical oral investigations》2020,24(8):2713-2725
Clinical Oral Investigations - The study evaluates the effect of adding graphene-Ag nanoparticles (G-AgNp) to a PMMA auto-polymerizing resin, with focus on antibacterial activity, cytotoxicity,... 相似文献
5.
Chendamarai E Balasubramanian P George B Viswabandya A Abraham A Ahmed R Alex AA Ganesan S Lakshmi KM Sitaram U Nair SC Chandy M Janet NB Srivastava VM Srivastava A Mathews V 《Blood》2012,119(15):3413-3419
Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring study on patients with APL treated with a single agent ATO regimen. A total of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy. 相似文献
6.
Evangelia Meimeti Nikolaos Tentolouris Christos Manes Chariclia Loupa Xeni Provatopoulou Dimitrios Mostratos Andreas Vitsos Vassilios Roussis Leonidas Tzouvelekis Vivi Miriagou Michail Rallis 《Wound repair and regeneration》2020,28(2):234-241
Diabetic foot ulceration is a common and severe complication of diabetes, causing substantial social, medical, and economic burdens. Treatment of foot ulcers remains challenging, thus requiring increasing awareness and more efficient management. This study investigates the efficacy of ointments, containing as main active ingredient the olive oil extract of the marine isopod Ceratothoa oestroides, in the treatment of patients with diabetic foot ulcers. Fifty‐two patients were allocated into four treatment groups either receiving therapy with an ointment containing extract of C. oestroides or extract of C. oestroides and eosin or extract of C. oestroides and cefaclor or no treatment. Patients were monitored for a period of 135 days by evaluation of transepidermal water loss, skin hydration, planimetry, photo‐documentation, and clinical condition. Treatment with the extract of C. oestroides demonstrated significant healing properties that became evident after 45 days of treatment and resulted in complete ulcer healing in 61% of the patients. A significant improvement in transepidermal water loss (p < 0.001), skin hydration levels (p < 0.001), and wound area (p < 0.001) was observed in all patients. Similar efficacy was demonstrated for the combination of C. oestroides extract with eosin treatment (p < 0.001). On the contrary, the combination of C. oestroides extract with cefaclor antibiotic agent completely inhibited the healing properties of the isopod extract and did not improve water loss, skin hydration, or wound area. An important factor for C. oestroides extract healing properties is its selective activity against Gram negative bacteria. Ointments containing C. oestroides extract alone or combined with the antimicrobial agent eosin emerges as an effective regimen for the treatment of diabetic foot ulcers. 相似文献
7.
8.
Kjersti J?rgensen Ruth Holm Gunhild M Maelandsmo Vivi Ann Fl?renes 《Clinical cancer research》2003,9(14):5325-5331
PURPOSE: The purpose of the present work was to analyze the protein expression of activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) in a panel of superficial spreading (SSM) and nodular (NM) primary and metastatic melanomas, and to correlate the expression level with clinicopathological parameters. EXPERIMENTAL DESIGN: Expression of activated ERK1/2 was examined by immunohistochemistry in 172 primary melanomas (108 SSM and 64 NMs), 67 metastatic lesions, and in 41 benign nevi. RESULTS: Fifty four percent of primary and 33% of metastatic melanomas expressed variable levels of activated ERK1/2. No immunoreactivity was detected in benign nevi. In 21% of the primaries only cytoplasmic expression was detected, whereas 3% and 30% showed positive immunoreactivity in either nucleus or cytoplasm and nucleus, respectively. Activated ERK1/2 expression varied significantly with the thickness of superficial spreading melanomas, with lower expression in thinner lesions (P = 0.016). A significant correlation between activated ERK1/2 and cyclin D1 (P = 0.031) in nodular, as well as between activated ERK1/2 and cyclin D3 (P = 0.030) in SSMs were observed. The protein level of p27(Kip1) correlated with activated ERK1/2 (P = 0.048) in the nucleus. Furthermore, a strong inverse correlation between activated ERK1/2 and membrane-bound beta-catenin (P = 0.004) in nodular melanomas was revealed. Activation of ERK1/2 did not have any impact on relapse-free or overall survival. CONCLUSION: Our results suggest that activation of ERK1/2 may be involved in cell cycle regulation in SSMs. Moreover, the inverse association between membrane-bound beta-catenin and ERK1/2 in NMs suggest that ERK1/2 activation may play a role in decreasing homotypic interactions through destabilization of beta-catenin. 相似文献
9.
Karine Flem Karlsen Erin McFadden Vivi Ann Flørenes Ben Davidson 《Gynecologic oncology》2019,152(2):408-415
Objective
The objective of this study was to analyze the expression level and clinical role of soluble AXL (sAXL) in cancers affecting the serosal surfaces, with focus on ovarian carcinoma.Methods
sAXL protein expression by ELISA was analyzed in 572 effusion supernatants, including 424 peritoneal, 147 pleural and 1 pericardial specimens.Results
sAXL was overexpressed in peritoneal effusions compared to pleural and pericardial specimens (p?<?0.001). sAXL levels were additionally significantly higher in effusions from patients with ovarian carcinoma, malignant mesothelioma and breast carcinoma compared to specimens from patients with other cancers (predominantly carcinomas of lung, gastrointestinal or uterine corpus/cervix origin) or benign reactive effusions (p?<?0.001). sAXL was further overexpressed in high-grade serous carcinoma (HGSC; n?=?373) compared to low-grade serous carcinoma (LGSC; n?=?32; p?=?0.036). In HGSC, sAXL levels were significantly lower in post-chemotherapy effusions compared to primary diagnosis pre-chemotherapy specimens (p?=?0.002). sAXL levels in HGSC were unrelated to chemoresponse at diagnosis, progression-free survival or overall survival. Levels were similarly unrelated to survival in LGSC and breast carcinoma.Conclusions
sAXL is widely expressed in malignant effusions, particularly in ovarian and breast carcinoma and in malignant mesothelioma. sAXL is overexpressed in HGSC compared to LGSC and its levels are lower following exposure to chemotherapy. However, sAXL levels are not informative of chemoresponse or survival. 相似文献10.
Antonio Vivi Maria Tassini Hava Ben-Horin Gil Navon Ofer Kaplan 《Breast cancer research and treatment》1997,43(1):15-25
Lonidamine (LND) is a relatively new anti-cancer drug,and several clinical trials have indicated that it may be effectivein combinations with other therapeutic modalities. LND isclassified within the metabolic inhibitor agents. Multidrugresistance (MDR) phenomenon is often associated with increasedenergy requirements, and enhanced glycolysis rate. These studieswere performed to delineate the mechanism of action of LNDon MDR human breast cancer cells, and to investigate whetherLND as a single agent, or in combination with anotheranti-metabolism drug, 2-deoxyglucose (2-DG), may be usefulagainst MDR tumors. The effects of LND on intact perfuseddrug-sensitive (WT) and 33-fold resistant to Adriamycin(Adr) MCF-7 cells, embedded in alginate micro capsules, were continuouslymonitored by 31P and 13C nuclearmagnetic resonance (NMR) spectroscopy. 31PNMR studies showed that LND induced intracellular acidificationand depletion of NTP in both WT and Adr cells. However, pH and NTPlevels decreased less in the Adr cells than in the WT cells(p < 0.05 for both parameters). 13CNMR demonstrated that LND inhibited lactate transport,and lactate signals were elevated in both cell lines. However, theintracellular lactate levels increased to a greater extentin the WT than in the Adr cells (p < 0.05).There were major differences in the effects of LND onmetabolism between sensitive and resistant cells.While LND enhanced glucose uptake in the WT cells, and itsadministration was followed by continuous increase oflactate signal, both processes were not affected by LNDin the Adr cells. 2-DG is a glucose analogue that inhibitsboth cellular uptake and utilization of glucose, leading to cell starvation. Combined treatment with LND and2-DG yielded at best additive, but not synergistic,cellular toxicity, and the metabolic effects of LNDwere attenuated by 2-DG. These results showed that the principalmechanism of action of LND is inhibition of lactate transportleading to intracellular lactate accumulation and acidificationin both WT and Adr cells. The Adr cells were only 2-fold resistantto LND (compared to the WT cells), and since cellular uptakeof alkaloid chemotherapy is improved in acidic environment,LND may have a role in the treatment protocols of MDR tumors,especially when given as the initial means for inductionof intracellular acidification. 相似文献