全文获取类型
收费全文 | 274篇 |
免费 | 16篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 4篇 |
妇产科学 | 3篇 |
基础医学 | 47篇 |
口腔科学 | 1篇 |
临床医学 | 37篇 |
内科学 | 52篇 |
皮肤病学 | 2篇 |
神经病学 | 34篇 |
特种医学 | 7篇 |
外科学 | 19篇 |
预防医学 | 32篇 |
眼科学 | 10篇 |
药学 | 9篇 |
肿瘤学 | 31篇 |
出版年
2023年 | 3篇 |
2022年 | 1篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 18篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 7篇 |
2013年 | 15篇 |
2012年 | 19篇 |
2011年 | 19篇 |
2010年 | 7篇 |
2009年 | 6篇 |
2008年 | 18篇 |
2007年 | 14篇 |
2006年 | 11篇 |
2005年 | 18篇 |
2004年 | 17篇 |
2003年 | 15篇 |
2002年 | 13篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1997年 | 6篇 |
1996年 | 3篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1964年 | 1篇 |
1946年 | 2篇 |
1928年 | 1篇 |
排序方式: 共有290条查询结果,搜索用时 15 毫秒
1.
2.
Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis 总被引:53,自引:0,他引:53
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Schoppmann SF Birner P Stöckl J Kalt R Ullrich R Caucig C Kriehuber E Nagy K Alitalo K Kerjaschki D 《The American journal of pathology》2002,161(3):947-956
Formation of lymphatic metastasis is the initial step of generalized spreading of tumor cells and predicts poor clinical prognosis. Lymphatic vessels generally arise within the peritumoral stroma, although the lymphangiopoietic vascular endothelial growth factors (VEGF)-C and -D are produced by tumor cells. In a carefully selected collection of human cervical cancers (stage pT1b1) we demonstrate by quantitative immunohistochemistry and in situ hybridization that density of lymphatic microvessels is significantly increased in peritumoral stroma, and that a subset of stromal cells express large amounts of VEGF-C and VEGF-D. The density of cells producing these vascular growth factors correlates with peritumoral inflammatory stroma reaction, lymphatic microvessel density, and indirectly with peritumoral carcinomatous lymphangiosis and frequency of lymph node metastasis. The VEGF-C- and VEGF-D-producing stroma cells were identified in situ as a subset of activated tumor-associated macrophages (TAMs) by expression of a panel of macrophage-specific markers, including CD68, CD23, and CD14. These TAMs also expressed the VEGF-C- and VEGF-D-specific tyrosine kinase receptor VEGFR-3. As TAMs are derived from monocytes in the circulation, a search in peripheral blood for candidate precursors of VEGFR-3-expressing TAMs revealed a subfraction of CD14-positive, VEGFR-3-expressing monocytes, that, however, failed to express VEGF-C and VEGF-D. Only after in vitro incubation with tumor necrosis factor-alpha, lipopolysaccharide, or VEGF-D did these monocytes start to synthesize VEGF-C de novo. In conclusion VEGF-C-expressing TAMs play a novel role in peritumoral lymphangiogenesis and subsequent dissemination in human cancer. 相似文献
3.
Cornelis P. J. Vendrik Anne Marie J. Fichtinger-Schepman Wilhelmina C. M. van Dijk-Knijnenburg W. H. de Jong Anke C. E. van der Minnen Gerard de Groot Geert Frits Berends P. A. Steerenberg 《Cancer chemotherapy and pharmacology》1997,39(6):479-485
An IgM immunocytoma cell line sensitive to cis-diamminedichloroplatinum(II) (CDDP) and a subline with acquired resistance were grown in LOU/M rats. In a previous study
with such rats that had been treated with a high dose of CDDP (10 mg/kg) the tumors did not show differences in cellular platinum
content or DNA-adduct levels, either immediately after treatment or 24 h later. Recently, this high dose was found to overcome
resistance. Therefore, the study was repeated with a 10-fold lower dose (1 mg/kg, i.v.). At 1 and 24 h after treatment, tumor
and kidney tissue were assayed for cellular platinum (atomic absorption spectroscopy, AAS) and DNA platination (immunochemical
detection of the four CDDP-DNA adducts). The results were compared with previous data. All tissues showed a linear response
to dose with regard to platinum uptake as well as adduct formation, with no quantitative difference being seen between the
tumors. Also the relative occurrence of the four adducts was very similar. Between 1 and 24 h, in tumors a substantial decrease
occurred in both platinum content and adduct level; the kidneys showed little reduction, if any. At the lower CDDP dose a
somewhat larger loss of platinum and removal of DNA adducts was observed for the resistant tumor, but these differences could
be explained by “dilution”, as this tumor continues to grow after low-dose treatment (about 20% within 24 h). Since the strong
difference observed between the tumors in sensitivity to CDDP cannot be attributed to differences in CDDP uptake, efficiency
of adduct formation, or repair capability, other mechanisms are held responsible.
Received 10 August 1995 / Accepted: 14 August 1996 相似文献
4.
Adrienne H Brouwers Peter F A Mulders Pieter H M de Mulder Wim J M van den Broek Wilhelmina C A M Buijs Carola Mala Frank B M Joosten Egbert Oosterwijk Otto C Boerman Frans H M Corstens Wim J G Oyen 《Journal of clinical oncology》2005,23(27):6540-6548
PURPOSE: A previous activity dose-escalation study using 131I-labeled chimeric monoclonal antibody cG250 in patients with progressive metastatic renal cell carcinoma (RCC) resulted in occasional therapeutic responses. The present study was designed to determine the safety and therapeutic efficacy of two sequential high-dose treatments with 131I-cG250. PATIENTS AND METHODS: Patients (n = 29) with progressive metastatic RCC received a low dose of (131)I-cG250 for assessment of preferential targeting of metastatic lesions, followed by the first radioimmunotherapy (RIT) with 2220 MBq/m2 131I-cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low-dose 131I-cG250 (n = 20) was given 3 months later. When blood clearance was not accelerated, a second RIT of 131I-cG250 was administered at an activity-dose of 1110 MBq/m2 (n = 3) or 1665 MBq/m2 (n = 16). Patients were monitored weekly for toxicity, and tumor size was evaluated by computed tomography once every 3 months intervals. RESULTS: The maximum-tolerated dose (MTD) of the second RIT was 1,665 MBq/m2 because of dose-limiting hematological toxicity. Based on an intention-to-treat analysis, after two RIT treatments, the disease stabilized in five of 29 patients, whereas it remained progressive in 14 of 29 patients. Two patients received no RIT, and eight of 29 received only one 131I-cG250 RIT because of grade 4 hematologic toxicity, formation of human antichimeric antibodies, or disease progression. CONCLUSION: In patients with progressive end-stage RCC, the MTD of the second treatment was 75% of the MTD of the first RIT. In the majority of patients, two cycles of 131I-cG250 could be safely administered without severe toxicity. No objective responses were observed, but occasionally two RIT doses resulted in stabilization of previously progressive disease. 相似文献
5.
6.
Wilhelmina?J.?den Boogert Hugo?A.?van Elteren Tom?G.?Goos Irwin?K.?M.?Reiss Rogier?C.?J.?de JongeEmail author Victor?J.?van den Berg 《Journal of clinical monitoring and computing》2018,32(3):457-464
The aim was to assess the reproducibility of the Pleth Variability Index (PVI), developed for non-invasive monitoring of peripheral perfusion, in preterm neonates below 32 weeks of gestational age. Three PVI measurements were consecutively performed in stable, comfortable preterm neonates in the first 48 h of life. On each occasion, pulse oximeter sensors were attached to two different limbs for 5 min. Reproducibility was assessed with the intra-class correlation coefficient (ICC) and Bland–Altman analysis. A total of 25 preterm neonates were included. Inter-limb comparison showed fair to moderate ICC’s with 95%-confidence intervals (95%-CI). Left hand–right hand ICC?=?0.498, 95%-CI (0.119–0.753); right foot–right hand ICC?=?0.314 (?0.088–0.644); right foot–left foot ICC?=?0.315 (?0.089–0.628). Intra-limb comparison showed fair to moderate ICC for right foot–right foot ICC?=?0.380 (?0.014–0.677); and good ICC for right hand–right hand ICC?=?0.646 (0.194–0.852). Bland–Altman plots showed moderate reproducibility of measurements between different limbs and of the same limb in consecutive time periods, with large biases and wide limits of agreement. The findings from this study indicate that PVI measurement is poorly reproducible when measured on different limbs and on the same limb in stable and comfortable preterm neonates. 相似文献
7.
8.
9.
Erin L. Boespflug James C. Eliassen Jonathan A. Dudley Marcelle D. Shidler Wilhelmina Kalt Suzanne S. Summer 《Nutritional neuroscience》2018,21(4):297-305
Objectives: Preclinical studies have shown that blueberry supplementation can improve cognitive performance and neural function in aged animals and have identified associations between anthocyanins and such benefits. Preliminary human trials also suggest cognitive improvement in older adults, although direct evidence of enhancement of brain function has not been demonstrated. In this study, we investigated the effect of blueberry supplementation on regional brain activation in older adults at risk for dementia.Methods: In a randomized, double-blind, placebo-controlled trial we performed pre- and post-intervention functional magnetic resonance imaging during a working memory (WM) task to assess the effect of blueberry supplementation on blood oxygen level-dependent (BOLD) signal in older adults with mild cognitive impairment, a risk condition for dementia.Results: Following daily supplementation for 16 weeks, blueberry-treated participants exhibited increased BOLD activation in the left pre-central gyrus, left middle frontal gyrus, and left inferior parietal lobe during WM load conditions (corrected P?0.01). There was no clear indication of WM enhancement associated with blueberry supplementation. Diet records indicated no between-group difference in anthocyanin consumption external to the intervention.Discussion: These data demonstrate, for the first time, enhanced neural response during WM challenge in blueberry-treated older adults with cognitive decline and are consistent with prior trials showing neurocognitive benefit with blueberry supplementation in this at-risk population. 相似文献
10.
Daniela Dünn-Kittenplon Asaf Ashkenazy-Titelman Inna Kalt Jean-Paul Lellouche Yaron Shav-Tal Ronit Sarid 《Viruses》2021,13(4)
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related herpesvirus. Like other herpesviruses, the KSHV icosahedral capsid includes a portal vertex, composed of 12 protein subunits encoded by open reading frame (ORF) 43, which enables packaging and release of the viral genome into the nucleus through the nuclear pore complex (NPC). Capsid vertex-specific component (CVSC) tegument proteins, which directly mediate docking at the NPCs, are organized on the capsid vertices and are enriched on the portal vertex. Whether and how the portal vertex is selected for docking at the NPC is unknown. Here, we investigated the docking of incoming ORF43-null KSHV capsids at the NPCs, and describe a significantly lower fraction of capsids attached to the nuclear envelope compared to wild-type (WT) capsids. Like WT capsids, nuclear envelope-associated ORF43-null capsids co-localized with different nucleoporins (Nups) and did not detach upon salt treatment. Inhibition of nuclear export did not alter WT capsid docking. As ORF43-null capsids exhibit lower extent of association with the NPCs, we conclude that although not essential, the portal has a role in mediating the interaction of the CVSC proteins with Nups, and suggest a model whereby WT capsids can dock at the nuclear envelope through a non-portal penton vertex, resulting in an infection ‘dead end’. 相似文献