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41.
Basi DL Adhikari N Mariash A Li Q Kao E Mullegama SV Hall JL 《American journal of physiology. Heart and circulatory physiology》2007,292(1):H516-H521
Redox factor-1 (Ref-1) is a multifunctional protein that regulates redox, DNA repair, and the response to cell stress. We previously demonstrated that Ref-1(+/-) mice exhibit a significantly reduced Ref-1 mRNA and protein levels within the vasculature, which are associated with increased oxidative stress. The goal of this study was to test the hypothesis that partial loss of Ref-1 altered the cellular response to vascular injury. Fourteen days after femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in Ref-1(+/-) mice compared with that in wild-type mice (P < 0.01). Bromodeoxyuridine labeling and transferase-mediated dUTP nick-end labeling staining at 14 days did not differ in the Ref-1(+/-) mice. In vitro studies found no significant changes in either serum-induced proliferation or baseline apoptosis in Ref-1(+/-) vascular smooth muscle cells. Exposure to Fas ligand; however, did result in increased susceptibility of Ref-1(+/-) vascular smooth muscle cells to apoptosis (P < 0.001). Ref-1(+/-) mice exhibited an increase in circulating baseline levels of IL-10, IL-1alpha, and VEGF compared with those in wild-type mice but a marked impairment in these pathways in response to injury. In sum, loss of a single allele of Ref-1 is sufficient to reduce intimal lesion formation and to alter circulating cytokine and growth factor expression. 相似文献
42.
Ami E Nakahara K Sato A Nguyen JT Hidaka K Hamada Y Nakatani S Kimura T Hayashi Y Kiso Y 《Bioorganic & medicinal chemistry letters》2007,17(15):4213-4217
We designed several HIV protease inhibitors with various d-cysteine derivatives as P(2)/P(3) moieties based on the structure of clinical drug candidate, KNI-764. Herein, we report their synthesis, HIV protease inhibitory activity, HIV IIIB cell inhibitory activity, cellular toxicity, and inhibitory activity against drug-resistant HIV strains. KNI-1931 showed distinct selectivity against HIV proteases and high potency against drug-resistant strains, surpassing those of Ritonavir and Nelfinavir. 相似文献
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Background
The lymphatic system complements the blood circulatory system in absorption and transport of nutrients, and in the maintenance of homeostasis. Angiopoietins 1 and 2 (Ang1 and Ang2) are regulators of both angiogenesis and lymphangiogenesis through the Tek/Tie-2 receptor tyrosine kinase. The response of endothelial cells to stimulation with either Ang1 or Ang2 is thought to be dependent upon the origin of the endothelial cells. In this study, we examined the effects of the angiopoietins on lymphatic, venous and arterial primary endothelial cells (bmLEC, bmVEC and bmAEC, respectively), which were isolated and cultured from bovine mesenteric vessels.Results
BmLEC, bmVEC and bmAEC cell populations all express Tie-2 and were shown to express the appropriate cellular markers Prox-1, VEGFR3, and Neuropilin-1 that define the particular origin of each preparation. We showed that while bmLECs responded slightly more readily to angiopoietin-2 (Ang2) stimulation, bmVECs and bmAECs were more sensitive to Ang1 stimulation. Furthermore, exposure of bmLECs to Ang2 induced marginally higher levels of proliferation and survival than did exposure to Ang1. However, exposure to Ang1 resulted in higher levels of migration in bmLECs than did to Ang2.Conclusion
Our results suggest that although both Ang1 and Ang2 can activate the Tie-2 receptor in bmLECs, Ang1 and Ang2 may have distinct roles in mesenteric lymphatic endothelial cells. 相似文献46.
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Moore V Kanu A Byron O Campbell G Danson MJ Hough DW Crennell SJ 《Extremophiles : life under extreme conditions》2011,15(3):327-336
Using citrate synthase from the hyperthermophile Pyrococcus furiosus (PfCS) as our test molecule, we show through guanidine hydrochloride-induced unfolding that the dimer separates into folded,
but inactive, monomers before individual subunit unfolding takes place. Given that forces across the dimer interface are vital
for thermostability, a robust computational method was derived that uses the University of Houston Brownian Dynamics (UHBD)
program to calculate both the hydrophobic and electrostatic contribution to the dimerisation energy at 100°C. The results
from computational and experimental determination of the lowered stability of interface mutants were correlated, being both
of the same order of magnitude and placing the mutant proteins in the same order of stability. This computational method,
optimised for hyperthermophilic molecules and tested in the laboratory, after further testing on other examples, could be
of widespread use in the prediction of thermostabilising mutations in other oligomeric proteins for which dissociation is
the first step in unfolding. 相似文献
50.
Leonard H Glasson E Nassar N Whitehouse A Bebbington A Bourke J Jacoby P Dixon G Malacova E Bower C Stanley F 《PloS one》2011,6(3):e17875