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971.
Wang HQ Imai Y Inoue H Kataoka A Iita S Nukina N Takahashi R 《Journal of neurochemistry》2008,107(1):171-185
Parkin, a ubiquitin ligase, is responsible for autosomal recessive juvenile parkinsonism (AR-JP). We identified parkin-associated endothelin receptor-like receptor (Pael-R) as a substrate of parkin, whose accumulation is thought to induce unfolded protein response (UPR) -mediated cell death, leading to dopaminergic neurodegeneration. To create an animal model of AR-JP, we generated parkin knockout/Pael-R transgenic (parkin-ko/Pael-R-tg) mice. parkin-ko/Pael-R-tg mice exhibited early and progressive loss of dopaminergic as well as noradrenergic neurons without formation of inclusion bodies, recapitulating the pathological features of AR-JP. Evidence of activation of UPR and up-regulation of dopamine and its metabolites were observed throughout the lifetime. Moreover, complex I activity of mitochondria isolated from parkin-ko/Pael-R-tg mice was significantly reduced later in life. These findings suggest that persistent induction of unfolded protein stress underlies chronic progressive catecholaminergic neuronal death, and that dysfunction of mitochondrial complex I and oxidative stress might be involved in the progression of Parkinson's disease. parkin-ko/Pael-R-tg mice represents an AR-JP mouse model displaying chronic and selective loss of catecholaminergic neurons. 相似文献
972.
973.
Kikuchi H Ishiko S Oshima Y Gokan N Hosaka K Kubohara Y 《Biochemical and biophysical research communications》2008,377(3):1012-1017
The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule (chlorinated alkylphenone) that induces stalk cell differentiation in the cellular slime mold Dictyostelium discoideum. In addition, DIF-1 and its derivatives have been shown to possess anti-leukemic activity and glucose consumption-promoting activity in vitro in mammalian cells. In this study, to assess the chemical structure-effect relationship of DIF-1, we synthesized eight derivatives of DIF-1 and investigated their stalk cell-inducing activity in Dictyostelium cells and pharmacological activities in mammalian cells. Of the derivatives, two amide derivatives of DIF-1, whose hydrophobic indexes are close to that of DIF-1, induced stalk cell differentiation as strongly as DIF-1 in Dictyostelium cells. It was also found that some derivatives suppressed cell growth in human K562 leukemia cells and promoted glucose consumption in mouse 3T3-L1 cells. These results give us valuable information as to the chemical structure-effect relationship of DIF-1. 相似文献
974.
Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease 总被引:2,自引:0,他引:2
Nakao I Kanaji S Ohta S Matsushita H Arima K Yuyama N Yamaya M Nakayama K Kubo H Watanabe M Sagara H Sugiyama K Tanaka H Toda S Hayashi H Inoue H Hoshino T Shiraki A Inoue M Suzuki K Aizawa H Okinami S Nagai H Hasegawa M Fukuda T Green ED Izuhara K 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(9):6262-6269
Excessive production of airway mucus is a cardinal feature of bronchial asthma and chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality in these diseases. IL-13, a Th2-type cytokine, is a central mediator in the pathogenesis of bronchial asthma, including mucus overproduction. Using a genome-wide search for genes induced in airway epithelial cells in response to IL-13, we identified pendrin encoded by the SLC26A4 (PDS) gene as a molecule responsible for airway mucus production. In both asthma and COPD mouse models, pendrin was up-regulated at the apical side of airway epithelial cells in association with mucus overproduction. Pendrin induced expression of MUC5AC, a major product of mucus in asthma and COPD, in airway epithelial cells. Finally, the enforced expression of pendrin in airway epithelial cells in vivo, using a Sendai virus vector, rapidly induced mucus overproduction in the lumens of the lungs together with neutrophilic infiltration in mice. These findings collectively suggest that pendrin can induce mucus production in airway epithelial cells and may be a therapeutic target candidate for bronchial asthma and COPD. 相似文献
975.
976.
977.
Komiya Y Kurabe N Katagiri K Ogawa M Sugiyama A Kawasaki Y Tashiro F 《The Journal of biological chemistry》2008,283(27):18753-18764
978.
Yoneyama M Nishiyama N Shuto M Sugiyama C Kawada K Seko K Nagashima R Ogita K 《Neurochemistry international》2008,52(4-5):761-769
Acute treatment with trimethyltin chloride (TMT) produces neuronal damage in the hippocampal dentate gyrus of mice. We investigated the in vivo role of glutathione in mechanisms associated with TMT-induced neural cell damage in the hippocampus by examining mice depleted of endogenous glutathione by prior treatment with 2-cyclohexen-1-one (CHO). In the hippocampus of animals treated with CHO 1h beforehand, a significant increase was seen in the number of single-stranded DNA-positive cells in the dentate gyrus when determined on day 2 after the injection of TMT at a dose of 2.0 mg/kg. Immunoblot analysis revealed that CHO treatment induced a significant increase in the phosphorylation of c-Jun N-terminal kinase in the cytosolic and nuclear fractions obtained from the dentate gyrus at 16 h after the TMT injection. There was also a concomitant increase in the level of phospho-c-Jun in the cytosol at 16 h after the injection. Expectedly, lipid peroxidation was increased by TMT in the hippocampus, and was enhanced by the CHO treatment. Moreover, CHO treatment facilitated behavioral changes induced by TMT. Taken together, our data indicate that TMT-induced neuronal damage is caused by activation of cell death signals induced at least in part by oxidative stress. We conclude that endogenous glutathione protectively regulates neuronal damage induced by TMT by attenuating oxidative stress. 相似文献
979.
Tomohiko Yamada Tomoshige Sugiyama Nana Tamaki Atsushi Kawakita Makoto Kato 《BMC evolutionary biology》2009,9(1):145-14
Background
The seacoasts of the Japanese Arc are fringed by many gravel beaches owing to active tectonic uplift and intense denudation caused by heavy rainfall. These gravel beaches are inhabited by gobies of the genus Luciogobius that burrow into the gravel sediment and live interstitially. Although their habitat and morphology (e. g., reduced fins, elongated, scale-less body, and highly segmented vertebral column) are highly unusual among fishes, little is known on how their morphological evolution has facilitated the colonization of interstitial habitats and promoted extensive diversification. We conducted thorough sampling of Luciogobius and related species throughout Japan, and performed molecular phylogenetic analysis to explore the patterns of morphological evolution associated with gravel beach colonization. 相似文献980.
E Takashiro Y Nakamura S Miyamoto Y Ozawa A Sugiyama K Fujimoto 《Bioorganic & medicinal chemistry》1999,7(9):2105-2114
The synthesis and the SAR study of novel pseudo symmetric inhibitors of HIV-1 protease are described. Michael addition of amino acid derivatives to vinyl ketones was utilized to derive a potent (nM) series of HIV-1 protease inhibitors. 相似文献