全文获取类型
收费全文 | 265篇 |
免费 | 27篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 5篇 |
妇产科学 | 10篇 |
基础医学 | 47篇 |
口腔科学 | 3篇 |
临床医学 | 20篇 |
内科学 | 79篇 |
皮肤病学 | 2篇 |
神经病学 | 27篇 |
特种医学 | 5篇 |
外科学 | 16篇 |
预防医学 | 8篇 |
眼科学 | 4篇 |
药学 | 26篇 |
肿瘤学 | 38篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 5篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 8篇 |
2014年 | 5篇 |
2013年 | 10篇 |
2012年 | 16篇 |
2011年 | 14篇 |
2010年 | 6篇 |
2009年 | 7篇 |
2008年 | 12篇 |
2007年 | 14篇 |
2006年 | 10篇 |
2005年 | 23篇 |
2004年 | 13篇 |
2003年 | 17篇 |
2002年 | 19篇 |
2001年 | 12篇 |
2000年 | 6篇 |
1999年 | 11篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 9篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有292条查询结果,搜索用时 15 毫秒
1.
Human lymphoblastoid cells produce extracellular matrix-degrading enzymes and induce endothelial cell proliferation, migration, morphogenesis, and angiogenesis 总被引:11,自引:0,他引:11
A. Vacca D. Ribatti M. Iurlaro A. Albini M. Minischetti F. Bussolino A. Pellegrino R. Ria M. Rusnati M. Presta V. Vincenti M. G. Persico F. Dammacco 《International Journal of Clinical & Laboratory Research》1998,28(1):55-68
Human lymphoproliferative diseases can be hypothesized to invade locally and to metastatize via mechanisms similar to those
developed by a variety of solid tumors, i.e., the secretion of extracellular matrix-degrading enzymes and stimulation of angiogenesis.
To assess this hypothesis, Namalwa, Raji, and Daudi cell lines (Burkitt’s lymphoma), LIK and SB cell lines (B-cell lymphoblastic
leukemia), CEM and Jurkat cell lines (T-cell lymphoblastic leukemia), and U266 cell line (multiple myeloma) were evaluated
for their capacity to produce matrix metalloproteinase-2 and -9, and urokinase-type plasminogen activator. These cell lines
were also assessed for their ability: (1) to produce the angiogenic basic fibroblast growth factor and vascular endothelial
growth factor; (2) to induce an angiogenic phenotype in cultured endothelial cells, represented by cell proliferation, chemotaxis,
and morphogensis; (3) to stimulate angiogenesis in different in vivo experimental models. All cell lines expressed the mRNA
for one or both metalloproteinases. Namalwa, Raji, LIK, SB, and U266 cells secreted the active form of both metalloproteinases,
while Daudi, CEM, and Jurkat cells produced metalloproteinase-2 but not -9. In contrast, urokinase-type plasminogen activator
was secreted only by SB cells. While Raji, LIK, SB, CEM, and Jurkat cells secreted both basic fibroblast growth factor and
vascular endothelial growth factor, Daudi and U266 cells produced only the former, and Namalwa cells only the latter. Accordingly,
the conditioned medium of all cell lines stimulated cell proliferation and/or chemotaxis in cultured endothelial cells, with
the exception of that of Namalwa cells which was ineffective. The conditioned medium of CEM and Jurkat cells induced morphogenesis
in cultured endothelial cells grown on a reconstituted basement membrane (Matrigel). Lastly, Namalwa, Raji, LIK, SB, U266,
CEM, and Jurkat cells induced angiogenesis and mononuclear cell recruitment in the murine Matrigel sponge model and in a chick
embryo chorioallantoic membrane assay. The extent of angiogenesis in both models was strictly correlated with the density
of the mononuclear cell infiltrate. The results indicate that human lymphoproliferative disease cells possess both local and
remote invasive ability via the secretion of matrix-degrading enzymes and the induction of angiogenesis which is fostered
by host inflammatory cells and by an intervening ensemble of angiogenic factors. 相似文献
2.
Jurjees Hasan Steven D Shnyder Andrew R Clamp Alan T McGown Roy Bicknell Marco Presta Michael Bibby John Double Steven Craig David Leeming Kenneth Stevenson John T Gallagher Gordon C Jayson 《Clinical cancer research》2005,11(22):8172-8179
BACKGROUND: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. RESULTS: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing > or =16 saccharide residues were investigated. CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin. 相似文献
3.
4.
5.
Mapping the CD4 binding site for human immunodeficiency virus by alanine-scanning mutagenesis. 总被引:18,自引:6,他引:18
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A Ashkenazi L G Presta S A Marsters T R Camerato K A Rosenthal B M Fendly D J Capon 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(18):7150-7154
Infection of mononuclear cells by human immunodeficiency virus (HIV) begins with binding of the viral envelope glycoprotein, gp120, to its receptor, CD4. CD4 contains four extracellular immunoglobulin-like domains, the first of which (V1) is sufficient for HIV binding. V1 contains three sequences homologous to the antigen-complementarity-determining regions (CDR1 to -3) of immunoglobulin variable domains. While all three immunoglobulin CDRs are involved in antigen binding, only amino acids within and flanking the CDR2-like region of CD4 have been shown previously to be involved in gp120 binding. To investigate whether other regions in V1 take part in gp120 binding, we substituted alanine for each of 64 amino acids, including all of the hydrophilic residues in this domain. Mutations at four locations outside the CDR2-like sequence (amino acids 29, 59-64, 77-81, and 85) markedly affected gp120 binding, but not the overall structure of V1 as probed with eight conformationally sensitive monoclonal antibodies. Thus, the gp120-binding site of CD4 is not limited to the CDR2-like sequence and consists of several discontinuous segments. Several amino acids were identified that are critical for the conformation of V1; the importance of these residues suggests some differences in the folding of this domain compared to immunoglobulin variable domains. Three amino acid substitutions were found that increase the affinity for gp120 significantly (1.7- to 2-fold individually and 4.2-fold when combined), suggesting that it may be possible to improve the HIV-blocking ability of CD4-based molecules by increasing their gp120 binding affinity. 相似文献
6.
7.
Proteomic analysis of human thyroid cell lines reveals reduced nuclear localization of Mn-SOD in poorly differentiated thyroid cancer cells 总被引:1,自引:0,他引:1
Russo D Bisca A Celano M Talamo F Arturi F Scipioni A Presta I Bulotta S Ferretti E Filetti S Scaloni A Damante G Tell G 《Journal of endocrinological investigation》2005,28(2):137-144
Differential protein arrays between nuclear extracts of human thyroid cell lines obtained from tumors with different degree of differentiation were exploited to define molecular alterations occurring during thyroid tumor progression. Nuclear extracts from the well differentiated TPC-1 (from papillary carcinoma) and the poorly differentiated ARO (from anaplastic carcinoma) cells showed an overall similar pattern of protein expression as revealed by two-dimensional gel electrophoresis analysis. However, manganese-superoxide dismutase (Mn-SOD) was clearly identified by mass spectrometry procedures as significantly less expressed in ARO compared to TPC-1 cells. A reduced expression of Mn-SOD in the nuclear compartment was confirmed by Western blot and immunofluorescence analysis. A similar expression pattern of nuclear Mn-SOD was detected by immunohistochemistry in human thyroid tumors, with the lowest or absent detection in anaplastic carcinomas. Moreover, the levels of nuclear Mn-SOD in tumor cells were lower than in the normal thyrocytes. These data indicate that an altered nuclear expression of Mn-SOD parallels, together with changes in other elements of the antioxidant protective system, the loss of differentiation occurring during the progression of thyroid tumors. 相似文献
8.
Roberto Ronca Patrizia Alessi Daniela Coltrini Emanuela Di Salle Arianna Giacomini Daria Leali Michela Corsini Mirella Belleri Chiara Tobia Cecilia Garlanda Elisa Bonomi Regina Tardanico William Vermi Marco Presta 《The Journal of pathology》2013,230(2):228-238
Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone (DHT) up‐regulates FGF2 and FGF8b production in murine TRAMP‐C2 prostate cancer cells, activating a FGF‐dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin‐3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N‐terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3‐derived pentapeptide Ac‐ARPCA‐NH2 abolish the mitogenic response of murine TRAMP‐C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT‐activated TRAMP‐C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP‐C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP‐C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP‐C2 cells overexpress only the FGF‐binding N‐terminal PTX3 domain. In keeping with the anti‐tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high‐grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti‐angiogenic and anti‐neoplastic activity in prostate cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
9.
Paolo Ditonno Roberto Ria Ilaria Marech Annunziata De Luisi Simona Berardi Maria Antonia Frassanito Emanuele Angelucci Daniele Derudas Giorgina Specchia Paola Curci Vincenzo Pavone Bernardo Rossini Domenico Ribatti Barbara Bottazzi Alberto Mantovani Marco Presta Franco Dammacco Angelo Vacca 《The Journal of pathology》2013,229(1):87-98
Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high affinity and selectivity to fibroblast growth factor‐2 (FGF2), thus inhibiting its pro‐angiogenic activity. Here we investigated the effects of PTX3 on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patient‐derived bone marrow (BM) plasma cells (PCs), endothelial cells (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross‐talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was evaluated by ELISA. Functional studies, including cell viability, wound healing, chemotaxis, and Matrigel® assays, were performed on MGUS and MM ECs and FBs upon the PTX3 treatment. Through western blot PTX3‐induced modulation in FGF2/FGF receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through western blot. Co‐cultures between MM ECs/FBs and human PC lines were used to evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were studied by flow cytometry. PTX3 provides a direct time‐ and dose‐dependent apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC lines. PTX3 inhibits migration of MM ECs and FBs in a dose‐dependent manner, and impacts in vitro and in vivo FGF2‐mediated MM angiogenesis. Co‐cultures of PCs and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and adhesion. We conclude that PTX3 is an anti‐angiogenic factor in MM and behaves as a cytotoxic molecule on MM cells by inhibiting the cross‐talk between PCs and ECs/FBs. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
10.
Bortoluzzi MC Passador-Santos F Capella DL Manfro G Nodari RJ Presta AA 《Annali di stomatologia》2012,3(1):11-13
Eosinophilic Ulcer (EU) is a rare self-limiting chronic benign lesion of the oral mucosa with pathogenesis still unclear, however it may resemble malignancies, traumatic ulcerations and some infections such as deep fungal infections, tuberculosis and primary syphilis. This is a case report of a patient with EU in the lateral border of the tongue with no history of associated trauma and refractory to treatment with drugs. The ulcer rapidly healed after an incisional biopsy and the definite diagnosis was achieved only combining histologic findings and the clinical follow-up. 相似文献