全文获取类型
收费全文 | 401篇 |
免费 | 47篇 |
国内免费 | 12篇 |
专业分类
儿科学 | 2篇 |
妇产科学 | 3篇 |
基础医学 | 36篇 |
临床医学 | 57篇 |
内科学 | 67篇 |
皮肤病学 | 1篇 |
神经病学 | 7篇 |
特种医学 | 2篇 |
外科学 | 13篇 |
综合类 | 47篇 |
预防医学 | 8篇 |
眼科学 | 1篇 |
药学 | 48篇 |
中国医学 | 2篇 |
肿瘤学 | 166篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 17篇 |
2020年 | 15篇 |
2019年 | 20篇 |
2018年 | 24篇 |
2017年 | 13篇 |
2016年 | 15篇 |
2015年 | 23篇 |
2014年 | 50篇 |
2013年 | 46篇 |
2012年 | 41篇 |
2011年 | 54篇 |
2010年 | 31篇 |
2009年 | 32篇 |
2008年 | 34篇 |
2007年 | 14篇 |
2006年 | 12篇 |
2005年 | 5篇 |
2004年 | 2篇 |
2003年 | 1篇 |
排序方式: 共有460条查询结果,搜索用时 15 毫秒
1.
Role of Plasmapheresis in the Management of Acute Kidney Injury in Patients With Multiple Myeloma: Should We Abandon It?
下载免费PDF全文
![点击此处可从《Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The aim of the current study was to determine whether plasmapheresis in combination with chemotherapy could significantly remove free light chains (FLC) in multiple myeloma (MM) patients with acute kidney injury (AKI) and therefore improve renal recovery and patient survival. During the study period, 29 patients with MM and AKI presented to our unit and were treated with two different therapy modalities (plasmapheresis with chemotherapy or bortezomib). At the end of treatment, a significant decrease of FLCs was present in the group treated with plasmapheresis compared to the bortezomib group. Patients treated with plasmapheresis had similar survival compared to patients treated with bortezomib. There was a significantly higher decrease of FLCs and longer survival in patients treated with three or more plasmapheresis sessions than in patients treated with two plasmapheresis sessions. Plasmapheresis therapy still remains a useful and effective method in the treatment of AKI in MM patients. Plasmapheresis significantly reduces FLCs compared to bortezomib especially with higher number of plasma exchange sessions but it must be combined with other chemotherapy agents in order to prolong renal recovery and therefore patient survival. 相似文献
2.
3.
《Biology of blood and marrow transplantation》2014,20(12):1899-1904
Bortezomib, a proteasome inhibitor capable of direct antitumor effects, has been shown to prevent acute graft-versus-host disease (GVHD) when administered in a short course immediately after bone marrow transplantation (BMT) in mice. However, when bortezomib is given continuously, CD4+ T cell–mediated gastrointestinal tract damage increases GVHD mortality. To investigate the protective effects of bortezomib on other organs, we used a CD8-dependent acute GVHD (aGVHD) model of C3H.SW donor T cells engrafted into irradiated C57BL/6 recipients (minor MHC mismatch), which lack significant gut GVHD. Our data in this model show that bortezomib can be given continuously to prevent and treat aGVHD mediated by CD8+ T cells, but this effect is organ specific, such that only skin, and not liver, protection was observed. Despite the lack of hepatic protection, bortezomib still significantly improved survival, primarily because of its skin protection. Reduced skin GVHD by bortezomib was correlated with reduced serum and skin IL-6 levels. Administration of a blocking IL-6 antibody in this model also resulted in similar cutaneous GVHD protection. These results indicate that bortezomib or blockade of IL-6 may prevent CD8+ T cell–mediated cutaneous acute GVHD. 相似文献
4.
《Toxicology in vitro》2015,30(8):1965-1976
E-cadherin/β-catenin complex plays an important role in maintaining the homeostasis of tissues and regulating cell proliferation, survival and apoptosis. To address the relationships between the change of E-cadherin/β-catenin complex and cell apoptosis, human oral squamous carcinoma SCC-25 cells were used to investigate whether the dissociation of the E-cadherin/β-catenin complex was the main reason of MG132- or bortezomib-induced apoptosis. We found that MG132 or bortezomib alone induced remarkable loss of cell integrity and contact, inhibited cell growth, survival, migration and caused cell cycle arrest, intracellular ROS production. Further experiments showed that colony formations were significantly decreased by MG132 and bortezomib alone or plus cis-diaminedichloroplatinum (CDDP). Immunofluorescence staining showed that SCC-25 cells exhibited remarkable accumulations of β-catenin in cytoplasm and few E-cadherin in cell membranes after MG132 or bortezomib treatment. Western blot results showed that MG132 or bortezomib induced high accumulation of ubiquitinated proteins and activation of apoptosis related protein caspase-3. Meanwhile, the combinational use of MG132 or bortezomib with CDDP led to synergistic effects on SCC-25 cells. However, knockdown of β-catenin could decrease MG132 or bortezomib induced cell death. Taken together, our data suggest that the regulation of E-cadherin/β-catenin complex could be a promising therapeutic target to overcome the multidrug resistance of oral cancer. 相似文献
5.
Wagenblast J Hambek M Baghi M Gstöttner W Strebhardt K Ackermann H Knecht R 《Journal of cancer research and clinical oncology》2008,134(3):323-330
Purpose
Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade®) in squamous cell carcinoma of the head and neck (SCCHN) cell lines and examined the interaction of the drug with docetaxel (TAX) and cisplatin (CDDP).Methods
Dose escalation studies were performed with eight squamous cell carcinoma cell lines using bortezomib alone or in combination with TAX or CDDP. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and western blot analysis.Results
Bortezomib alone showed a significant antiproliferative activity in all SCCHN cell lines (P = 0.012), and the activity was further enhanced by the addition of TAX or CDDP (P ≤ 0.036). When the combination of bortezomib and CDDP was used, the dose of the latter could be reduced to yield the same antiproliferative effect as the cytotoxic drug alone (P < 0.012).Conclusions
Our results indicate that bortezomib increases the cytotoxic activity of TAX and CDDP in SCCHN cell lines. In vivo and in the clinical setting, the addition of bortezomib may allow to reduce the doses of TAX or CDDP to decrease the systemic toxicity of these drugs.6.
《Advances in medical sciences》2021,66(1):21-27
PurposeProteasome inhibitors (PI) bortezomib or carfilzomib among them, play a crucial role in the modern standard therapy for multiple myeloma (MM). In this study, we intended to evaluate whether immunoproteasome (IMP) concentration could act as an effective biomarker which determines the probability of response to treatment with bortezomib, in order to detect groups of patients who are more likely to respond to treatment with PI.Materials and methodsIn our study, we evaluated IMP concentration in the plasma of 40 patients with monoclonal gammopathy of undetermined significance (MGUS) and 116 patients with newly diagnosed MM during treatment with or without PI.ResultsThe values of all the studied parameters after the applied chemotherapy in the responders’ group of patients declined considerably during the consecutive cycles of chemotherapy compared to their initial levels. On the contrary, in the group of non-responders, we observed no change in the measured IMP parameters during the consecutive cycles of therapy. We also showed that higher baseline IMP concentration might indicate longer overall survival (OS) in all patients.ConclusionsOur results indicate that assessing plasma IMP concentration can be applied as a strong biomarker for predicting clinical response to treatment and OS in patients with newly diagnosed MM. 相似文献
7.
8.
9.
Effect of bortezomib regimens and daratumumab monotherapy on cellular immunity in multiple myeloma patients
下载免费PDF全文
![点击此处可从《Iranian journal of immunology : IJI》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Background: Treatment with Bortezomib (a proteasome inhibitor) and Daratumumab (DARA, a monoclonal anti CD38 antibody) are effective in patients with multiple myeloma (MM). However, these drugs impair cellular immunity, which may render the patients more prone to infection. Objective: To investigate the effect of Bortezomib-based regimens and Daratumumab monotherapy on the lymphocyte subpopulations in MM patients. Methods: Peripheral blood samples were collected from 32 patients, including 29 newly diagnosed who treated with bortezomib regimens and 3 patients with relapsed and refractory MM treated with Daratumumab as monotherapy. The immunophenotypic analysis was performed by flow cytometry at baseline and during the third cycle of Bortezomib regimen and fourth week of Daratumumab treatment. Results: In the third cycle of Bortezomib, there was a significant decrease in CD3+ T cells, CD+4 T cells, memory T cells, and natural killer cells (NK cells). However, CD8+ T cells increased dramatically, followed by a significant reduction in the CD4/CD8 ratio. On the other hand, Daratumumab led to an increase in the T cell population after four weeks of treatment, with a significant increase in CD3+ T cells as well as CD4+ T cells, while NK cells were dramatically depleted in all patients. Conclusion: Bortezomib had a negative influence on subsets of T cells, while Daratumumab positively affected T cells subsets. In both treatments, NK cells decreased significantly. These results suggested that DARA is more specific to target myeloma cells than Bortezomib. Also, DARA expanded T cells especially CD3+ T cells and CD4+ T cells. 相似文献
10.
《Biology of blood and marrow transplantation》2014,20(12):1949-1957
Patients with multiple myeloma (MM) who relapse after autologous transplantation have limited therapeutic options. We conducted a prospective, multicenter, phase IIa study to investigate the safety and efficacy of i.v. busulfan (Bu) in combination with bortezomib as a conditioning regimen for a second autotransplantation. Because a safe Bu exposure was unknown in patients receiving this combination, Bu was initially targeted to a total area under the concentration–time curve (AUC) of 20,000 μM × minute. As no concentration-limiting toxicity was observed in 6 patients, this Bu exposure was utilized in the following treatment cohort (n = 24). Individualized Bu dose, based on test dose .8 mg/kg pharmacokinetics (PK), was administered daily for 4 consecutive days starting 5 days before transplantation, followed by a single dose of bortezomib (1.3 mg/m2) 1 day before transplantation. The total mean dose of i.v. Bu (including the test dose and 4-day administration) was 14.2 mg/kg (standard deviation = 2.48; range, 8.7 to 19.2). Confirmatory PK demonstrated that only 2 of 30 patients who underwent transplantation were dosed outside the Bu AUC target and dose adjustments were made for the last 2 doses of i.v. Bu. The median age was 59 years (range, 48 to 73). Median time from first to second transplantation was 28.0 months (range, 12 to 119). Of 26 evaluable patients, 10 patients attained a partial response (PR) or better at 3 months after transplantation, with 2 patients attaining a complete response. At 6 months after transplantation, 5 of 12 evaluable patients had maintained or improved their disease status. Median progression-free survival was 191 days, whereas median overall survival was not reached during the study period. The most common grade 3 and 4 toxicities were febrile neutropenia (50.0%) and stomatitis (43.3%). One transplantation-related death was observed. A combination of dose-targeted i.v. Bu and bortezomib induced PR or better in one third of patients with MM who underwent a second autotransplantation, with acceptable toxicity. 相似文献