首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   507篇
  完全免费   46篇
  2018年   48篇
  2017年   23篇
  2016年   17篇
  2015年   3篇
  2014年   38篇
  2013年   23篇
  2012年   21篇
  2011年   40篇
  2010年   19篇
  2009年   32篇
  2008年   30篇
  2007年   39篇
  2006年   26篇
  2005年   26篇
  2004年   21篇
  2003年   14篇
  2002年   14篇
  2001年   7篇
  2000年   11篇
  1999年   15篇
  1998年   11篇
  1997年   8篇
  1996年   6篇
  1995年   6篇
  1994年   11篇
  1993年   12篇
  1992年   6篇
  1991年   2篇
  1990年   4篇
  1989年   4篇
  1988年   4篇
  1987年   3篇
  1986年   1篇
  1985年   1篇
  1984年   1篇
  1982年   3篇
  1979年   1篇
  1976年   1篇
  1975年   1篇
排序方式: 共有553条查询结果,搜索用时 46 毫秒
1.
Vascular endothelial growth factor (VEGF) was originally identified as an endothelial cell specific growth factor stimulating angiogenesis and vascular permeability. Some family members, VEGF C and D, are specifically involved in lymphangiogenesis. It now appears that VEGF also has autocrine functions acting as a survival factor for tumour cells protecting them from stresses such as hypoxia, chemotherapy and radiotherapy. The mechanisms of action of VEGF are still being investigated with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins which were not previously associated with angiogenesis. VEGF plays an important role in embryonic development and angiogenesis during wound healing and menstrual cycle in the healthy adult. VEGF is also important in a number of both malignant and non-malignant pathologies. As it plays a limited role in normal human physiology, VEGF is an attractive therapeutic target in diseases where VEGF plays a key role. It was originally thought that in pathological conditions such as cancer, VEGF functioned solely as an angiogenic factor, stimulating new vessel formation and increasing vascular permeability. It has since emerged it plays a multifunctional role where it can also have autocrine pro-survival effects and contribute to tumour cell chemoresistance. In this review we discuss the established role of VEGF in angiogenesis and the underlying mechanisms. We discuss its role as a survival factor and mechanisms whereby angiogenesis inhibition improves efficacy of chemotherapy regimes. Finally, we discuss the therapeutic implications of targeting angiogenesis and VEGF receptors, particularly in cancer therapy.  相似文献
2.
Cryosurgery--a putative approach to molecular-based optimization   总被引:14,自引:0,他引:14  
3.
Gottesman MM  Ling V 《FEBS letters》2006,580(4):998-1009
The discovery and characterization of P-glycoprotein, an energy-dependent multidrug efflux pump, as a mechanism of multidrug resistance in cancer is generally accepted as a significant contribution to the ongoing effort to end death and suffering from this disease. The historical reflections of Victor Ling and Michael Gottesman concerning the early years of this research highlight the important contributions of the multidisciplinary teams involved in these studies, and illustrate how technological developments in biochemistry and molecular and cell biology enabled this discovery.  相似文献
4.
Microtubules,microtubule-interfering agents and apoptosis   总被引:13,自引:0,他引:13  
Microtubules are dynamic polymers that play crucial roles in a large number of cellular functions. Their pivotal role in mitosis makes them a target for the development of anticancer drugs. Microtubule-damaging agents suppress microtubule dynamics, leading to disruption of the mitotic spindle in dividing cells, cell cycle arrest at M phase, and late apoptosis. A better understanding of the processes coupling microtubule damage to the onset of apoptosis will reveal sites of potential intervention in cancer chemotherapy. Inhibition of microtubule dynamics induces persistent modification of biological processes (M arrest) and signaling pathways (mitotic spindle assembly checkpoint activation, Bcl-2 phosphorylation, c-Jun NH2-terminal kinase activation), which ultimately lead to apoptosis through the accumulation of signals that finally reach the threshold for the onset of apoptosis or through diminishing the threshold for engagement of cell death. Microtubules serve also as scaffolds for signaling molecules that regulate apoptosis, such as Bim and survivin, and their release from microtubules affect the activities of these apoptosis regulators. Thus, sustained modification of signaling routes and changes in the scaffolding properties of microtubules seem to constitute two major processes in the apoptotic response induced by microtubule-interfering agents.  相似文献
5.
Summary Cell cycle synchronization of tumor cells by exposure to hyperbaric oxygenation (HBO) may increase the efficacy of chemotherapy or radiation by placing cells into a chemosensitive portion of the cycle. The purpose of the current study was to examine oxygen pressure-dependent relationships with respect to the cell cycle in prostate tumor cells in vitro. LNCaP cells were grown in an incubator at 21% O2 and then exposed to 100% oxygen at pressures up to 6 atmospheres (atm) for 1.5 h. Cells were then returned to the incubator and evaluated for DNA content by propidium iodide and new DNA synthesis with a pulse-chase experiment. Cell cycle effects were evaluated by flow cytometry. Exposure to HBO increased the percentage of cells synthesizing new DNA in a dose-dependent fashion: 0 atm, 44%; 6 atm, 65%. Cells that synthesize new DNA accumulate in G2/M as a function of partial pressure of oxygen. These results suggest that HBO induces cells to enter the cell cycle and accumulate in G2/M. Cell cycle synchronization and entry of senescent cells into the cell cycle suggest that HBO may be a useful adjuvant to chemotherapy or radiation in the treatment of prostate cancer. There are two potential mechanisms of action that may make HBO efficacious in the treatment of prostate cancer. HBO may potentiate cancer chemotherapeutic agents that cause damage to DNA during DNA synthesis or HBO may inhibit cell division causing accumulation in G2/M.  相似文献
6.
The role of p53 in treatment responses of lung cancer   总被引:11,自引:0,他引:11  
Resistance to radio- and chemotherapy is a major problem in treatment responses of lung cancer. In this disease, biological markers, that can be predictive of response to treatment for guiding clinical practice, still need to be validated. Radiotherapy and most chemotherapeutic agents directly target DNA and in response to such therapies, p53 functions as a coordinator of the DNA repair process, cell cycle arrest, and apoptosis. In fact, it participates in the main DNA repair systems operative in cells, including NHEJ, HRR, NER, BER, and MMR. Given the high p53 mutation frequency in lung cancer which likely impairs some of the p53-mediated functions, a role of p53 as a predictive marker for treatment responses has been suggested. In this review, we summarize the conflicting results coming from preclinical and clinical studies on the role of p53 as a predictive marker of responses to chemotherapy or radiotherapy in lung cancer.  相似文献
7.
Rhythms in human gastrointestinal mucosa and skin   总被引:11,自引:0,他引:11  
Rhythmicity in cell proliferation is well established in the gastrointestinal tract and skin, both in rodents and humans. This is the basis for studies on the timing of both chemotherapy and radiotherapy. More recently, circadian rhythm studies of cell-cycle proteins have confirmed earlier findings based on thymidine labeling and flow cytometry. The genetic control of circadian rhythms has been elucidated recently and a possible connection between the circadian clock and the timing of cell-cycle events has been suggested. The data for gastrointestinal mucosa and skin are reviewed and the potential clinical implications of these results are discussed.  相似文献
8.
1. Osmotic opening of the blood–brain barrier by intracarotid infusion of a hypertonic arabinose or mannitol solution is mediated by vasodilatation and shrinkage of cerebrovascular endothelial cells, with widening of the interendothelial tight junctions to an estimated radius of 200 Å. The effect may be facilitated by calcium-mediated contraction of the endothelial cytoskeleton.2. The marked increase in apparent blood–brain barrier permeability to intravascular substances (10-fold for small molecules) following the osmotic procedure is due to both increased diffusion and bulk fluid flow across the tight junctions. The permeability effect is largely reversed within 10 min.3. In experimental animals, the osmotic method has been used to grant wide access to the brain of water-soluble drugs, peptides, antibodies, boron compounds for neutron capture therapy, and viral vectors for gene therapy. The method also has been used together with anticancer drugs to treat patients with metastatic or primary brain tumors, with some success and minimal morbidity.  相似文献
9.
10.
The Mechanism of Action of Multidrug-Resistance-Linked P-Glycoprotein   总被引:9,自引:0,他引:9  
P-glycoprotein (Pgp), the ATP-binding cassette (ABC) transporter, confers multidrug resistance to cancer cells by extruding cytotoxic natural product amphipathic drugs using the energy of ATP hydrolysis. Our studies are directed toward understanding the mechanism of action of Pgp and recent work deals with the assessment of interaction between substrate and ATP sites and elucidation of the catalytic cycle of ATP hydrolysis. The kinetic analyses of ATP hydrolysis by reconstituted purified Pgp suggest that ADP release is the rate-limiting step in the catalytic cycle and the substrates exert their effect by modulating ADP release. In addition, we provide evidence for two distinct roles for ATP hydrolysis in a single turnover of Pgp, one in the transport of drug and the other in effecting conformational changes so as to reset the transporter for the next catalytic cycle. Detailed kinetic measurements determined that both nucleotide-binding domains behave symmetrically and during individual hydrolysis events the ATP sites are recruited in a random manner. Furthermore, only one nucleotide site hydrolyzes ATP at any given time, causing (in this site) a conformational change that drastically decreases (>30-fold) the affinity of the second site for ATP-binding. Thus, the blocking of ATP-binding to the second site while the first one is in catalytic conformation appears to be the basis for the alternate catalytic cycle of ATP hydrolysis by Pgp, and this may be applicable as well to other ABC transporters linked with the development of multidrug resistance.  相似文献
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号