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991.
Yan Yang Peng-Yun LiJun Cheng Fang CaiMing Lei Xiao-Qiu TanMiao-Ling Li Zhi-Fei LiuXiao-Rong Zeng 《Biochemical and biophysical research communications》2013
Large conductance Ca2+-activated K+ channel (BKCa) is a potential target for coronary artery-relaxing medication, but its functional regulation is largely unknown. Here, we report that inositol trisphosphate (IP3) activated BKCa channels in isolated porcine coronary artery smooth muscle cells and by which decreased the coronary artery tone. Both endogenous and exogenous IP3 increased the spontaneous transient outward K+ currents (STOC, a component pattern of BKCa currents) in perforated and regular whole-cell recordings, which was dependent on the activity of IP3 receptors. IP3 also increased the macroscopic currents (MC, another component pattern of BKCa currents) via an IP3 receptor- and sarcoplasmic Ca2+ mobilization-independent pathway. In inside-out patch recordings, direct application of IP3 to the cytosolic side increased the open probability of single BKCa channel in an IP3 receptor-independent manner. We conclude that IP3 is an activator of BKCa channels in porcine coronary smooth muscle cells and exerts a coronary artery-relaxing effect. The activation of BKCa channels by IP3 involves the enhancement of STOCs via IP3 receptors and stimulation of MC by increasing the Ca2+ sensitivity of the channels. 相似文献
992.
Sebastian de Vries Isabel S. Naarmann-de Vries Henning Urlaub Hongqi Lue Jürgen Bernhagen Dirk H. Ostareck Antje Ostareck-Lederer 《The Journal of biological chemistry》2013,288(8):5815-5827
Vascular endothelial growth factor A (VEGF) is a crucial proangiogenic factor, which regulates blood vessel supply under physiologic and pathologic conditions. The VEGF mRNA 5′-untranslated region (5′-UTR) bears internal ribosome entry sites (IRES), which confer sustained VEGF mRNA translation under hypoxia when 5′-cap-dependent mRNA translation is inhibited. VEGF IRES-mediated initiation of translation requires the modulated interaction of trans-acting factors. To identify trans-acting factors that control VEGF mRNA translation under hypoxic conditions we established an in vitro translation system based on human adenocarcinoma cells (MCF-7). Cytoplasmic extracts of MCF-7 cells grown under hypoxia (1% oxygen) recapitulate VEGF IRES-mediated reporter mRNA translation. Employing the VEGF mRNA 5′-UTR and 3′-UTR in an RNA affinity approach we isolated interacting proteins from translational active MCF-7 extract prepared from cells grown under normoxia or hypoxia. Interestingly, mass spectrometry analysis identified the DEAD-box RNA helicase 6 (DDX6) that interacts with the VEGF mRNA 5′-UTR. Recombinant DDX6 inhibits VEGF IRES-mediated translation in normoxic MCF-7 extract. Under hypoxia the level of DDX6 declines, and its interaction with VEGF mRNA is diminished in vivo. Depletion of DDX6 by RNAi further promotes VEGF expression in MCF-7 cells. Increased secretion of VEGF from DDX6 knockdown cells positively affects vascular tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. Our results indicate that the decrease of DDX6 under hypoxia contributes to the activation of VEGF expression and promotes its proangiogenic function. 相似文献
993.
Accumulation of transglutaminase 2 (TG2) is often associated with mineral deposits in vasculature. Here, we demonstrate that purified TG2 stimulated a 3-fold increase in matrix mineralization and up-regulation of osteoblastic markers in cultured primary vascular smooth muscle cells (VSMCs). Extracellular TG2 interacts with the low density lipoprotein related-protein 5 receptor and activates beta-catenin signaling in VSMCs. These results suggest that TG2 may promote vascular calcification by activating the beta-catenin signaling pathway. 相似文献
994.
Ying Zhang Hui Zhang Pengfei Yu Qian Liu Kun Liu Huiying Duan Ginling Luan Kazumi Yagasaki Guoying Zhang 《Cytotechnology》2009,59(3):191-200
The purpose of this study is to investigate in vitro and ex vivo effects of matrine on the growth of human lung cancer and
hepatoma cells and the cancer cell migration as well as the expressions of related proteins in the cancer cells. Matrine significantly
inhibited the in vitro and ex vivo growth of human non-small cell lung cancer A549 and hepatoma SMMC-7721 cells. Matrine induced
the apoptosis in A549 and SMMC-7721 cells. Western blot analysis indicated that matrine dose-dependently down-regulated the
expression of anti-apoptotic protein Bcl-2 and up-regulated the level of pro-apoptotic protein bax, eventually leading the
reduction of ratios of Bcl-2/Bax proteins in A549 and SMMC-7721 cells. Furthermore, matrine significantly suppressed the A549
cell migration without reducing the cell viability. In addition, matrine dramatically reduced the secretion of vascular endothelial
growth factor A in A549 cells. More importantly, matrine markedly enhanced the anticancer activity of anticancer agent trichostatin
A (the histone deacetylase inhibitor) by strongly reducing the viability and/or the ratio of Bcl-2/Bax protein in A549 cells.
Our findings suggest that matrine may have the broad therapeutic and/or adjuvant therapeutic application in the treatment
of human non-small cell lung cancer and hepatoma. 相似文献
995.
Protease-activated receptor 2 (PAR2) is a G-protein coupled receptor that is cleaved and activated by serine proteases including the coagulation protease factor VIIa (FVIIa). There is evidence that PAR2 function contributes to angiogenesis, but the mechanisms involved are poorly defined. Here we show that PAR2 activation in human breast cancer cells leads to the upregulation of vascular endothelial growth factor (VEGF). Activation of PAR2 with agonist peptide (AP), trypsin or FVIIa results in a robust increase of VEGF message and protein. Incubation of cells with PAR1-AP, PAR3-AP, PAR4-AP, or thrombin has only a modest effect on VEGF production. Cleavage blocking antibodies show that FVIIa-mediated VEGF production is PAR2 mediated. Mitogen-activated protein kinase (MAPK) pathway inhibitors U0126 and SB203580 inhibit PAR2-mediated VEGF production. Incubation of cells with PAR2-AP leads to significant extracellular regulated kinase1/2 (ERK1/2) and p38 MAPK phosphorylation and activation. Collectively, these data suggest that PAR2 signaling through MAPK pathways leads to the production of proangiogenic VEGF in breast cancer cells. 相似文献
996.
Trion A Schutte-Bart C Bax WH Jukema JW van der Laarse A 《Molecular and cellular biochemistry》2008,308(1-2):25-33
Background Vascular calcification is an organized process in which vascular smooth muscle cells (VSMCs) are implicated primarily. The
purpose of the present study was to assess the effects of calcium antagonists and statins on VSMC calcification in vitro.
Methods VSMC calcification was stimulated by incubation in growth medium supplemented with 10 mmol/l β-glycerophosphate, 8 mmol/l
CaCl2, 10 mmol/l sodium pyruvate, 1 μmol/l insulin, 50 μg/ml ascorbic acid, and 100 nmol/l dexamethasone (calcification medium).
Calcification, proliferation, and apoptosis of VSMCs were quantified. Results Calcium deposition was stimulated dose-dependently by β-glycerophosphate, CaCl2, and ascorbic acid (all P < 0.01). Addition of amlodipine (0.01–1 μmol/l) to the calcification medium did not affect VSMC calcification. However, atorvastatin
(2–50 μmol/l) stimulated calcium deposition dose-dependently. Combining treatments stimulated calcification to a degree similar
to that observed with atorvastatin alone. Both atorvastatin and amlodipine inhibited VSMC proliferation at the highest concentration
used. Only atorvastatin (50 μmol/l) induced considerable apoptosis of VSMCs. Conclusion In vitro calcification of VSMCs is not affected by amlodipine, but is stimulated by atorvastatin at concentrations ≥10 μmol/l,
which could contribute to the plaque-stabilizing effect reported for statins.
J. W. Jukema is an Established Clinical Investigator of The Netherlands Heart Foundation 2001D032. 相似文献
997.
弱激光对脂质体介导的血管平滑肌细胞基因转染的影响 总被引:3,自引:0,他引:3
本研究采用阳离子脂质体介导外源基因转染体外培养的兔血管平滑肌细胞(SMC),在基因转染过程中给予激光照射,用细胞化学染色方法测定基因转染阳性率。结果显示:用510.6nm激光于基因转染前,以功率密度1mw/cm2,能量密度2、4、6J/cm2和5mW/cm2,4、6J/cm2;及10mW/cm2,2J/cm2进行照射均能显著提高基因转染率(p<0.05);于基因转染后即刻以功率密度1mW/cm2、能量密度2J/cm2和5mW/cm2、6J/cm2照射也能提高基因转染率(p<0.05)。而用627.8nm激光照射对基因转染率无显著影响 相似文献
998.
999.
Induction of Fibronectin (FN) gene expression by platelet-derived growth factor (PDGF) isoforms in rat thoracic aortic smooth muscle cells (SMC) was examined. PDGF-BB enhances FN levels in SMC cultures in a time- and concentration-response fashion. PDGF-AA and PDGF-AB show no effect on FN levels. The effects of insulin and insulin-like growth factor-I (IGF-I) on PDGF-BB-induced FN levels were examined. No additivity of FN levels is observed between PDGF-BB and insulin and/or IGF-I. Experiments also show that PDGF-BB enhances FN mRNA levels, implying that acquisition of additional FN mRNA units accounts for the increase in FN levels. Induction of FN and FN mRNA levels by PDGF-BB could be one of the initial events in vascular SMC proliferation and extracellular matrix expansion, leading to atherosclerosis and hypertension. 相似文献
1000.
A suite of muscarinic receptor blockers was used to characterize the receptor(s) mediating the contractile effect of acetylcholine (ACh) on isolated rings of ventral aorta from the dogfish shark, Squalus acanthias. The M2/M4-specific inhibitor N,N’-bis(6-{[(2-methoxyphenyl) methyl] amino} hexyl) -1,8- octane diamine tetrahydrochloride (methoctramine) did not reduce the efficacy of ACh, and the M3-specific inhibitor 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) displaced the ACh concentration-response curve to the right at much lower concentrations than the M1-specific inhibitor (5-11-dihydro-11- [4-methyl-l-piperazinyl)acetyl] -6H-pyrido[2,3-b] [1,4] benzodiazepin-6-one dihydrochloride) (pirenzepine). It appears, therefore, that an M3-type muscarinic receptor is expressed in the aortic vascular smooth muscle of the dogfish shark. 相似文献