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61.
62.
目的观察表皮生长因子(EGF)在小鼠肾脏远端小管发育中的表达,探讨其在小鼠肾脏远端小管发育中的作用。方法采用免疫组化、免疫荧光、Western blot技术结合体视学分析方法检测生后1、3、5、6、7、14、21、28和40天小鼠肾脏远端小管EGF的表达特征。结果EGF于生后6d开始出现在肾皮、髓质交界处的远直小管上皮细胞,之后随着日龄的增加其表达量逐渐增加,表达于皮、髓质远直小管,21天同成年鼠表达于远直小管和远曲小管第一段。结论EGF对小鼠肾脏远端小管的分化、生长发育起重要作用。 相似文献
63.
Masahito Shimizu Yohei Shirakami Hiroyasu Sakai Hideharu Tatebe Takayuki Nakagawa Yukihiko Hara I. Bernard Weinstein Hisataka Moriwaki 《Cancer letters》2008
The receptor tyrosine kinase (RTK) insulin like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) axis plays an important role in the development of hepatocellular carcinoma (HCC). EGCG inhibits activation of the various types of RTKs and that this is associated with inhibition of multiple downstream signaling pathways. In this study we examined the effects of EGCG on activity of the IGF/IGF-1R axis in HepG2 human HCC cells which express constitutive activation of this axis. The level of phosphorylated (i.e. activated) form of the IGF-1R protein (p-IGF-1R) was increased in a series of human HCC cell lines when compared with the Hc normal human hepatocytes. EGCG preferentially inhibited growth of HepG2 cells when compared with Hc cells. Treatment of HepG2 cells with EGCG induced apoptosis and caused a decrease in the p-IGF-1R protein and its downstream signaling molecules including the p-ERK, p-Akt, p-Stat-3, and p-GSK-3β proteins, both in the absence or presence of ligand stimulation. EGCG also decreased the levels of both IGF-1 and IGF-2 proteins and mRNAs, but increased the levels of the IGFBP-3 protein. These findings suggest that EGCG can overcome the stimulatory effects of IGFs on the IGF-1R dependent signaling pathway, thus expanding the roles of EGCG as an inhibitor of critical RTKs involved in HCC cell proliferation. These results provide further evidence that EGCG may be useful in the chemoprevention or treatment of liver cancer. 相似文献
64.
Jianxin Lu Y. Peng Z.J. Zheng J.H. Pan Yangde Zhang Yidong Bai 《Cancer letters》2008,260(1-2):187-197
We report here the generation and characterization of EGF-IL-18 fusion protein as an anti-tumor reagent. The epidermal growth factor (EGF) and interleukin-18 (IL-18) fusion protein was shown to induce interferon-γ (IFNγ) expression and secretion in KG-1 cells, and to promote PBMNC proliferation. It also stimulated activation of CD4+ T cells, and increased other immune responses. Moreover, EGF-IL-18 could induce significant tumor regression in SMMC-7721-xenografted Balb/c nude mice when administered together with peritumoral injection of X-ray-irradiated NK-92 cells, and this regression is associated with arresting of the tumor cells in G1 phase and induction of apoptosis. 相似文献
65.
目的分析小鼠肝细胞内胰岛素与表皮生长因子(EGF)信号转导磷蛋白质组的动力学行为差别,以此找出两者关键性的信号蛋白。方法采用双向电泳及放射性同位素标记技术,进行分析比较EGF与胰岛素分别介导的磷酸化蛋白质组的动力学行为。结果参与两者信号转导的磷蛋白质种类没有多大差异,大多数信号磷蛋白磷酸化水平的动力学行为也表现为一致性,但有4个蛋白点其磷酸化水平随时间变化趋势明显不同。结论胰岛素与EGF虽然在多方面有许多相似之处,但在同一细胞内参与信号转导的个别信号蛋白其磷酸化水平的动力学行为差别较大,估计这些蛋白就是导致EGF与胰岛素最终生物学活性有所不同的关键蛋白。 相似文献
66.
G. SCAMBIA P. BENEDETTI PANICI F. BATTAGLIA G. FERRANDINA C. GAGGINI S MANCUSO 《International journal of gynecological cancer》1991,1(6):253-258
Abstract. Scambia G, Benedetti Panici P, Battaglia F, Ferrandina G, Gaggini C, Mancuso S. Presence of epidermal growth factor (EGF) receptor and proliferative response to EGF in six human ovarian carcinoma cell lines. Int J Gynecol Cancer 1991; 1 : 253–258.
We investigated the role of the EGF-EGFR system as a regulator of ovarian cancer cell growth. In five (OVCA 433, OV 166, OV 1225, OV RS 1000, JA1) of six ovarian cancer cell lines examined we showed the presence of a single high-affinity125 I-EGF binding site with Kd varying from 0.24 to 0.86 nM and a number of binding sites/cell from 9700 to 75 000. In OVCA 433, OV 166, and OV RS 1000 cells we demonstrated a low-affinity 125 I-EGF binding site with Kd ranging from 1.10 to 2.12 nM.
TR-170 cells lacked the EGF binding and were unresponsive to EGF in terms of cell proliferation while all EGFR+ cells except JA 1 exhibited a proliferative response to EGF. Moreover, the growth response of the four EGF-sensitive cell lines showed different patterns since at high EGF concentrations (100 ng ml−1 ) there was no longer a stimulatory effect in OV 1225, OV 166, and OV RS 1000 cells while the mitogenic activity was still present in OVCA 433 cells.
Our results demonstrate that EGF plays a role in regulating ovarian cancer cell growth. However, the presence of EGFR is not a perfect indicator of the EGFR system functionality. The cell lines we have examined could be useful models to clarify the mechanism of EGF action and the role played by the EGF system in the onset and spread of ovarian tumors. 相似文献
We investigated the role of the EGF-EGFR system as a regulator of ovarian cancer cell growth. In five (OVCA 433, OV 166, OV 1225, OV RS 1000, JA1) of six ovarian cancer cell lines examined we showed the presence of a single high-affinity
TR-170 cells lacked the EGF binding and were unresponsive to EGF in terms of cell proliferation while all EGFR+ cells except JA 1 exhibited a proliferative response to EGF. Moreover, the growth response of the four EGF-sensitive cell lines showed different patterns since at high EGF concentrations (100 ng ml
Our results demonstrate that EGF plays a role in regulating ovarian cancer cell growth. However, the presence of EGFR is not a perfect indicator of the EGFR system functionality. The cell lines we have examined could be useful models to clarify the mechanism of EGF action and the role played by the EGF system in the onset and spread of ovarian tumors. 相似文献
67.
Summary A primary cell culture of endometriotic cells was established to examine the hormonal regulation of endometriosis. The addition
of estradiol had no effect on the DNA synthesis of cultured endometriotic cells. Progesterone at 10−7 M caused a significant reduction in the amount of the DNA synthesis. An inhibitory effect of progesterone was completely
eliminated by the concomitant addition of RU486, an antiprogesterone. The addition of epidermal growth factor (EGF) at 1 ng/ml
significantly increased the DNA synthesis. Other growth factors, such as fibroblast growth factor and insulin-like growth
factor also produced a modest but significant increase in DNA synthesis. These results seem to provide clues for clarifying
the pathophysiology of endometriosis. 相似文献
68.
Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research 总被引:23,自引:0,他引:23
H. Shelton Earp Thomas L. Dawson Xiong Li Hong Yu 《Breast cancer research and treatment》1995,35(1):115-132
Summary The EGF receptor (EGFR) and HER2 are members of a growth factor receptor family. Overexpression of either protein in advanced breast cancer correlates with poor prognosis. EGF stimulates growth by binding to EGFR, activating the receptor's intracellular tyrosine kinase. The initial consequence is phosphorylation of specific tyrosine-containing sequences in the receptor's carboxyl terminus. These phosphotyrosines serve as high affinity recognition sites for proteins that, in turn, transmit the growth signal inside the cell. Mechanistic studies suggest that EGF binds to a single EGFR, triggering dimerization with another like receptor molecule. This dimerization is thought to initiate the tyrosine kinase activation.The EGF receptor family was recently expanded with the sequencing of HER3 and HER4. Each of the four family members was postulated to regulate a unique growth or differentiation signaling repertoire when activated by a receptor-specific ligand. However, new data from numerous laboratories suggest that EGFR family members may play a complex and ultimately more flexible role in signaling by forming heterodimers between family members, e.g. EGFR:HER2 or HER4:HER2. These heterodimers may form even when only one member of the pair binds its ligand.This review summarizes current work on heterodimerization and attempts to predict the consequences for downstream signaling. In brief, when compared to ligand-dependent receptor homodimers comprised of two proteins with the same internalization sequence and phosphorylated tyrosine residues, heterodimers are likely to: i) expand substrate selection and downstream signaling pathway activation; ii) promote interaction between sets of substrates in the mixed receptor complexes that would not ordinarily be physically juxtaposed; iii) alter the duration of receptor signaling by changing rates of receptor internalization, ligand loss, kinase inactivation, recycling, etc.; and iv) alter rates of receptor and substrate dephosphorylation. In addition to understanding interactions of heterodimers with the internalization machinery, identification of receptor-specific substrates and binding proteins for each EGFR family member will be necessary to explicate the role of heterodimers in growth and differentiation. 相似文献
69.
A. Gompel A. Martin P. Simon D. Schöevaert G. Plu-Bureau D. Hugol J. Audouin E. Leygue J. B. Truc Ph. Poitout 《Breast cancer research and treatment》1996,38(2):227-235
Summary EGF receptor (EGF-R) and c-erbB-2 are homologous tyrosine kinase transmembrane receptors. They are involved in controlling proliferation, and probably differentiation, of normal breast epithelial cells, and their expression has been linked to the prognosis of breast cancer. Their physiological roles in normal breast tissue remain to be elucidated, as most studies to date have involved breast cancer cell lines. We studied the location of EGF-R and c-erbB-2 in 100 samples of normal breast with standard immunohistochemical methods and double-labelling techniques. EGF-R was mainly expressed on the stroma and myoepithelial cells, whereas c-erbB-2 expression was exclusively epithelial. An image analyser was used to quantitate variations in their expression during the mentrual cycle. EGF-R and c-erbB-2 expression on epithelial cells was stronger during the luteal phase than the follicular phase (p < 0.01 for EGF-R). The pattern of expression was also compared with that in 28 breast cancers and 7 fibroadenomas. 相似文献
70.