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101.
102.
Mauricio Lopez-Obando Ambre Guillory Franois-Didier Boyer David Cornu Beate Hoffmann Philippe Le Bris Jean-Bernard Pouvreau Philippe Delavault Catherine Rameau Alexandre de Saint Germain Sandrine Bonhomme 《The Plant cell》2021,33(11):3487
In angiosperms, the α/β hydrolase DWARF14 (D14), along with the F-box protein MORE AXILLARY GROWTH2 (MAX2), perceives strigolactones (SL) to regulate developmental processes. The key SL biosynthetic enzyme CAROTENOID CLEAVAGE DIOXYGENASE8 (CCD8) is present in the moss Physcomitrium patens, and PpCCD8-derived compounds regulate moss extension. The PpMAX2 homolog is not involved in the SL response, but 13 PpKAI2LIKE (PpKAI2L) genes homologous to the D14 ancestral paralog KARRIKIN INSENSITIVE2 (KAI2) encode candidate SL receptors. In Arabidopsis thaliana, AtKAI2 perceives karrikins and the elusive endogenous KAI2-Ligand (KL). Here, germination assays of the parasitic plant Phelipanche ramosa suggested that PpCCD8-derived compounds are likely noncanonical SLs. (+)-GR24 SL analog is a good mimic for PpCCD8-derived compounds in P. patens, while the effects of its enantiomer (−)-GR24, a KL mimic in angiosperms, are minimal. Interaction and binding assays of seven PpKAI2L proteins pointed to the stereoselectivity toward (−)-GR24 for a single clade of PpKAI2L (eu-KAI2). Enzyme assays highlighted the peculiar behavior of PpKAI2L-H. Phenotypic characterization of Ppkai2l mutants showed that eu-KAI2 genes are not involved in the perception of PpCCD8-derived compounds but act in a PpMAX2-dependent pathway. In contrast, mutations in PpKAI2L-G, and -J genes abolished the response to the (+)-GR24 enantiomer, suggesting that PpKAI2L-G, and -J proteins are receptors for moss SLs. The study of moss PpKAI2L receptors for strigolactones and related compounds highlights MORE AXILLARY GROWTH2-dependent and -independent pathways for the perception of these compounds. 相似文献
103.
Bernard Barlaam Sabina Cosulich Martina Fitzek Hervé Germain Stephen Green Lyndsey L. Hanson Craig S. Harris Urs Hancox Kevin Hudson Christine Lambert-van der Brempt Maryannick Lamorlette Françoise Magnien Gilles Ouvry Ken Page Linette Ruston Lara Ward Bénédicte Delouvrié 《Bioorganic & medicinal chemistry letters》2017,27(13):3030-3035
We report the discovery of a novel aminopyrazine series of PI3Kα inhibitors, designed by hybridizing two known scaffolds of PI3K inhibitors. We describe the progress achieved from the first compounds plagued with poor general kinase selectivity to compounds showing high selectivity for PI3Kα over PI3Kβ and excellent general kinase selectivity. This effort culminated with the identification of compound 5 displaying high potency and selectivity, and suitable physiochemical and pharmacokinetic properties for oral administration. In vivo, compound 5 showed good inhibition of tumour growth (86% tumour growth inhibition at 50 mg/kg twice daily orally) in the MCF7 xenograft model in mice. 相似文献
104.
M Joyeux-Faure F Stanke-Labesque B Lefebvre P Béguin D Godin-Ribuot C Ribuot S H Launois G Bessard P Lévy 《Journal of applied physiology》2005,98(5):1691-1696
Coronary heart disease is frequently associated with obstructive sleep apnea syndrome and treating obstructive sleep apnea appears to significantly improve the outcome in coronary heart disease. Thus we have developed a rat model of chronic intermittent hypoxia (IH) to study the influence of this condition on myocardial ischemia-reperfusion tolerance and on functional vascular reactivity. Wistar male rats were divided in three experimental groups (n = 12 each) subjected to chronic IH (IH group), normoxia (N group), or control conditions (control group). IH consisted of repetitive cycles of 1 min (40 s with inspired O(2) fraction 5% followed by 20 s normoxia) and was applied for 8 h during daytime, for 35 days. Normoxic cycles were applied in the same conditions, inspired O(2) fraction remaining constant at 21%. On day 36, mean arterial blood pressure (MABP) was measured before isolated hearts were submitted to an ischemia-reperfusion protocol. The thoracic aorta and left carotid artery were also excised for functional reactivity studies. MABP was not significantly different between the three experimental groups. Infarct sizes (in percent of ventricles) were significantly higher in IH group (46.9 +/- 3.6%) compared with N (26.1 +/- 2.8%) and control (21.7 +/- 2.1%) groups. Vascular smooth muscle function was similar in aorta and carotid arteries from all groups. The endothelium-dependent relaxation in response to acetylcholine was also similar in aorta and carotid arteries from all groups. Chronic IH increased heart sensitivity to infarction, independently of a significant increase in MABP, and did not affect vascular reactivity of aorta and carotid arteries. 相似文献
105.
Barlaam B Acton DG Ballard P Bradbury RH Cross D Ducray R Germain H Hudson K Klinowska T Magnien F Ogilvie DJ Olivier A Ross HS Smith R Trigwell CB Vautier M Wright L 《Bioorganic & medicinal chemistry letters》2008,18(6):1799-1803
We have identified a new series of C-5 substituted indazolylaminoquinazolines as potent erbB2 kinase inhibitors. The lead compound 22 showed excellent in vitro potency, good physical properties, acceptable oral pharmacokinetics in rat and dog, and low human in vitro clearance. It showed at least equivalent activity dose for dose compared to lapatinib in various erbB2- or EGFR-driven xenograft models after chronic oral administration. 相似文献
106.
Alvarez S Pazos-Randulfe Y Khanwalkar H Germain P Alvarez R Gronemeyer H de Lera AR 《Bioorganic & medicinal chemistry》2008,16(22):9719-9728
A series of 9-cis-retinoic acid analogs modified at the hydrophobic ring with a (bi)cyclohexenyl moiety derived from natural terpenes has been stereoselectively prepared using a Suzuki cross-coupling as key step. Transient transactivation studies indicate that modification of the hydrophobic ring impacts dramatically on RXR-binding and transactivation, with most retinoids being inactive on RXRbeta, while preserving their RAR pan-agonist profile. Furthermore, only the RARgamma subtype was capable of enantiomeric discrimination with some pairs of enantiomeric terpene-retinoids. 相似文献
107.
108.
Jean-Marie Pétémanagnan Ouattara Lacina Coulibaly Seydou Tiho Germain Gourène 《Ecological Engineering》2009,35(8):1237-1242
To improve our understanding of the ecological functioning of constructed wetlands, the macrofauna structure in the sediments of a constructed wetland planted with Panicum maximum treating domestic wastewater was studied. Two beds were planted with young P. maximum and two unplanted beds were used as controls. After 150 days of wastewater treatment on the beds, macrofauna was collected by taking five cores of sediment samples at the corners and the centre of each bed following three layers in the vertical profile. Globally, the planted beds removed COD, NH4+, and PO43? more (p < 0.05) than the control. Eleven taxa belonging to 6 classes and 11 orders were recorded. Macrofauna was significantly more diversified (Mann–Whitney test: p < 0.05) in terms of Shannon index of diversity in the planted beds (0.25–0.44 bits/ind.) than in the control (0.08–0.23 bits/ind.). But macrofauna settlement presents a relative homogeneity between the beds (index Jaccard = 0.63). Its abundance was three times higher in the planted bed than in the control. From the surface to the bottom of the beds, macrofauna diversity and abundance decreased and were heavily dominated by Annelida. The significant relationships were only observed between Insecta and Myriapoda in the control. 相似文献
109.
Laurent Beck Christine Leroy Christine Sala��n Germain Margall-Ducos Chantal Desdouets G��rard Friedlander 《The Journal of biological chemistry》2009,284(45):31363-31374
PiT1 is a Na+-phosphate (Pi) cotransporter located at the plasma membrane that enables Pi entry into the cell. Its broad tissue expression pattern has led to the idea that together with the closely related family member PiT2, PiT1 is the ubiquitous supplier of Pi to the cell. Moreover, the role of Pi in phosphorylation reactions, ATP production, DNA structure, and synthesis has led to the view that Pi availability could be an important determinant of cell growth. However, these issues have not been clearly addressed to date, and the role of either Pi or PiT proteins in cell proliferation is unknown. Using RNA interference in HeLa and HepG2 cells, we show that transient or stable PiT1 depletion markedly reduces cell proliferation, delays cell cycle, and impairs mitosis and cytokinesis. In vivo, PiT1 depletion greatly reduced tumor growth when engineered HeLa cells were injected into nude mice. We provide evidence that this effect on cell proliferation is specific to PiT1 and not shared by PiT2 and is not the consequence of impaired membrane Na+-Pi transport. Moreover, we show that modulation of cell proliferation by PiT1 is independent from its transport function because the proliferation of PiT1-depleted cells can be rescued by non-transporting PiT1 mutants. PiT1 depletion leads to the phosphorylation of p38 mitogen-activated protein (MAP) kinase, whereas other MAP kinases and downstream targets of mammalian target of rapamycin (mTOR) remain unaffected. This study is the first to describe the effects of a Pi transporter in cell proliferation, tumor growth, and cell signaling. 相似文献
110.