全文获取类型
收费全文 | 895篇 |
免费 | 38篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 10篇 |
妇产科学 | 8篇 |
基础医学 | 214篇 |
口腔科学 | 23篇 |
临床医学 | 59篇 |
内科学 | 146篇 |
皮肤病学 | 26篇 |
神经病学 | 39篇 |
特种医学 | 9篇 |
外科学 | 77篇 |
综合类 | 38篇 |
预防医学 | 37篇 |
眼科学 | 17篇 |
药学 | 127篇 |
中国医学 | 49篇 |
肿瘤学 | 60篇 |
出版年
2023年 | 4篇 |
2022年 | 13篇 |
2021年 | 20篇 |
2020年 | 22篇 |
2019年 | 33篇 |
2018年 | 52篇 |
2017年 | 38篇 |
2016年 | 19篇 |
2015年 | 36篇 |
2014年 | 106篇 |
2013年 | 71篇 |
2012年 | 62篇 |
2011年 | 53篇 |
2010年 | 45篇 |
2009年 | 64篇 |
2008年 | 58篇 |
2007年 | 49篇 |
2006年 | 41篇 |
2005年 | 34篇 |
2004年 | 30篇 |
2003年 | 16篇 |
2002年 | 14篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 9篇 |
1996年 | 2篇 |
1995年 | 8篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
排序方式: 共有940条查询结果,搜索用时 31 毫秒
51.
The integrin family of cell adhesion molecules has multiple functions within the CNS 总被引:6,自引:0,他引:6
Integrins comprise a large family of cell adhesion molecules that mediate interactions between the extracellular environment and the cytoplasm. During the last decade, analysis of the expression and function of these molecules has revealed that integrins regulate many aspects of cell behavior including cell death, proliferation, migration, and differentiation. Within the central nervous system (CNS), most of the early studies focused on the role of integrins in mediating adhesive and migratory events in two distinct processes: neural development and CNS inflammation. Interestingly, recent analysis of transgenic mice has provided some surprising results regarding the role of integrins in neural development. Furthermore, a large body of evidence now supports the idea that in addition to these well-described functions, integrins play multiple roles in the CNS, both during development and in the adult in areas as diverse as synaptogenesis, activation of microglia, and stabilization of the endothelium and blood-brain barrier. Many excellent reviews have addressed the contribution of integrins in mediating leukocyte extravasation during CNS inflammation. This review will focus on recently emerging evidence of novel and diverse roles of integrins and their ligands in the CNS during development and in the adult, in health and disease. 相似文献
52.
SC1 is an extracellular matrix glycoprotein that is related to the multifunctional protein SPARC. These matricellular members play regulatory roles in modulating cellular interactions. SC1 expression is enriched in the central nervous system during embryonic and postnatal development as well as in the adult brain. In the rat cerebellum, SC1 is expressed at high levels in Bergmann glial cells and their radial fibers which project into the synaptic-rich molecular layer. At specific stages of development and in the adult, SC1 mRNA is selectively transported into cellular processes of these cells. In the present study, we have examined the effect of whole-body hyperthermia on the transport of SC1 mRNA in Bergmann glial cells of the rat cerebellum. Our results show that SC1 mRNA transport is diminished at 10 and 15 h post-hyperthermia, but returns to control levels by 24 h after heat shock. One of the characteristics of a heat shock on cells grown in tissue culture is a collapse of the cytoskeletal network. Intact components of the cytoskeleton are necessary for the transport of mRNA into peripheral processes of cells. However, in vivo hyperthermia does not appear to affect the morphology of the intermediate filament proteins GFAP, vimentin, or the beta-tubulin component of microtubules in Bergmann glial cell processes. During the hyperthermic time course, levels of vimentin protein increase, which is reflected by immunoreactivity of activated astrocytes and microvasculature in cerebellar white matter. 相似文献
53.
54.
SPARC is a multifunctional extracellular matrix glycoprotein that shares partial sequence homology with SC1. These extracellular matrix molecules are thought to play important roles in modulating cellular interactions. In vitro, SPARC has been shown to exhibit anti-adhesive activity. In the present investigation, in situ hybridization is used to compare the expression patterns of SC1 and SPARC mRNA in the rat embryo. Results show that SC1 and SPARC expression is spatially and temporally regulated. SC1 mRNA is strongly expressed in the embryonic brain and spinal cord, whereas SPARC mRNA is enriched in craniofacial cartilage and skeletal structures. This differential expression pattern in the rat embryo suggests that SC1 plays an important role in the developing nervous system, whereas SPARC participates primarily in events associated with skeletal development. However at embryonic day 17, SC1 and SPARC mRNA show parallel expression patterns in areas of the cerebellum undergoing cell migratory events. 相似文献
55.
56.
Cells exist within a complex tissue microenvironment, which includes soluble factors, extracellular matrix molecules, and neighboring cells. In the breast, the adhesive microenvironment plays a crucial role in driving both normal mammary gland development as well tumor initiation and progression. Researchers are designing increasingly more complex ways to mimic the in vivo microenvironment in an in vitro setting, so that cells in culture may serve as model systems for tissue structures. Here, we explore the use of microfabrication technologies to engineer the adhesive microenvironment of cells in culture. These new tools permit the culture of cells on well-defined surface chemistries, patterning of cells into defined geometries either alone or in coculture scenarios, and measurement of forces associated with cell-ECM interactions. When applied to questions in mammary gland development and neoplasia, these new tools will enable a better understanding of how adhesive, structural, and mechanical cues regulate mammary epithelial biology. 相似文献
57.
Pancreatic stellate cell migration: role of the phosphatidylinositol 3-kinase(PI3-kinase) pathway 总被引:9,自引:0,他引:9
McCarroll JA Phillips PA Kumar RK Park S Pirola RC Wilson JS Apte MV 《Biochemical pharmacology》2004,67(6):1215-1225
Pancreatic stellate cells (PSCs) are implicated as key mediators of pancreatic fibrogenesis and are found in increased numbers in areas of pancreatic injury. This increase in number may be due to increased local proliferation and/or migration of PSCs to affected areas from surrounding tissue. We have recently shown that PSCs can migrate and that this migration is stimulated by PDGF in a predominantly chemotactic manner [Gut 52 (2003) 677]. However, the signalling mechanisms responsible for PDGF-induced PSC migration are not known. Aims: (i) To determine whether PDGF-induced PSC migration is mediated by the PI3-kinase pathway. (ii) To investigate whether cell migration is influenced by cell proliferation and whether an interaction exists between the PI3-kinase pathway and the ERK1/2 pathway (known to mediate cell proliferation) in PSCs exposed to PDGF. Methods: (i) PI3-kinase activity was assessed by measuring the activation (phosphorylation) of its downstream substrate Akt in rat PSCs incubated with PDGF (10ng/mL) for 5min, 15min, 60min, and 24hr in the presence or absence of the specific PI3-kinase inhibitor wortmannin. (ii) The role of the PI3-kinase pathway in PSC migration was examined by assessing PSC migration through a porous membrane after exposure to PDGF in the presence and absence of wortmannin for 24hr. (iii) The relationship between migration and proliferation was assessed by examining migration of PSCs exposed to PDGF in the presence and absence of mitomycin C, an inhibitor of cell proliferation. (iv) The interaction between PI3-kinase and ERK1/2 was examined by incubation of PSCs with PDGF in the presence and absence of wortmannin, followed by assessment of ERK1/2 activation by western blot. Results: PDGF increased Akt activation in PSCs as early as at 5min of incubation and this increase was sustained for 24hr. Inhibition of PI3-kinase by wortmannin decreased basal as well as PDGF-induced migration and also inhibited ERK1/2 activation. Inhibition of PSC proliferation with mitomycin C significantly reduced (but did not abolish) basal and PDGF-induced PSC migration. Conclusions: (i) The PI3-kinase pathway is induced in PSCs after exposure to PDGF and this induction is sustained for at least 24hr. (ii) The PI3-kinase pathway plays a role in PDGF-induced PSC migration and is partially involved in mediating ERK1/2 activation. (iii) PSC migration is dependent, at least in part, on cell proliferation. 相似文献
58.
59.
Silzle T Randolph GJ Kreutz M Kunz-Schughart LA 《International journal of cancer. Journal international du cancer》2004,108(2):173-180
Development and progression of epithelial malignancies are frequently accompanied by complex phenotypic alterations of resident tissue fibroblasts. Some of these changes, such as myofibroblastic differentiation and an oncofetal extracellular matrix (ECM) expression profile, are also implicated in inflammation and tissue repair. Studies over the past decade revealed the relevance of reciprocal interactions between tumor cells and tumor-associated host fibroblasts (TAF) in the malignant process. In many tumors, a considerable fraction of the inflammatory infiltrate is located within the fibroblast- and ECM-rich stromal compartment. However, while fibroblasts are known as "sentinel cells" in various nonneoplastic diseases, where they often regulate the composition and function of recruited leucocytes, they are hardly considered active participants in the inflammatory host response in tumors. This article focuses on the functional impact of TAF on immune cells. The complex network of immune-modulating effects transduced by TAF and TAF-derived factors is highlighted, and recent reports that support the hypothesis that TAF are involved in the inflammatory response and immune suppression in tumors are reviewed. The role of TAF-dependent ECM remodeling and TAF-derived peptide growth factors, cytokines, and chemokines in the immune modulation is stressed and the idea of TAF as an important therapeutic target is emphasized. 相似文献
60.
Hepatic fibrosis results from excess extracellular matrix produced primarily by hepatic stellate cells (HSC). In response to injury, HSC differentiate to a myofibroblastic phenotype expressing smooth muscle actin and fibrillar collagens. Relaxin is a polypeptide hormone shown to have antifibrotic effects in fibrosis models. In this study, activated HSC from rat liver were treated with relaxin to determine if relaxin can reverse markers of HSC activation. Relaxin treatment resulted in a decrease in the expression of smooth muscle actin, but had no effect on cell proliferation rate. The levels of total collagen and type I collagen were reduced, while the synthesis of new collagen was inhibited. Furthermore, relaxin caused an increase in the expression and secretion of rodent interstitial collagenase (MMP-13), but there was no effect on the gelatinases MMP-2 or MMP-9. Relaxin also increased secretion of TIMP-1 and TIMP-2. The effective concentration of relaxin to induce these effects was consistent with action through the relaxin receptor. In conclusion, relaxin reversed markers of the activated phenotype of HSC including the production of fibrillar collagen. At the same time, the activity of a fibrillar collagenase was increased. These data suggest that relaxin not only inhibits HSC properties that contribute to the progression of hepatic fibrosis, but also promotes the clearance of fibrillar collagen. Therefore, relaxin may be a useful approach in the treatment of hepatic fibrosis. 相似文献