全文获取类型
收费全文 | 458篇 |
免费 | 18篇 |
专业分类
476篇 |
出版年
2022年 | 1篇 |
2021年 | 8篇 |
2020年 | 1篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 2篇 |
2016年 | 12篇 |
2015年 | 14篇 |
2014年 | 18篇 |
2013年 | 19篇 |
2012年 | 17篇 |
2011年 | 29篇 |
2010年 | 17篇 |
2009年 | 14篇 |
2008年 | 17篇 |
2007年 | 22篇 |
2006年 | 30篇 |
2005年 | 23篇 |
2004年 | 20篇 |
2003年 | 24篇 |
2002年 | 26篇 |
2001年 | 26篇 |
2000年 | 21篇 |
1999年 | 15篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 10篇 |
1989年 | 7篇 |
1988年 | 9篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1973年 | 2篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有476条查询结果,搜索用时 0 毫秒
81.
Huy NT Serada S Trang DT Takano R Kondo Y Kanaori K Tajima K Hara S Kamei K 《Journal of biochemistry》2003,133(5):693-698
Plasmodium falciparum histidine-rich protein 2 (PfHRP2) has been suggested to be an initiator of the polymerization of heme, which is produced as by-product on the digestion of hemoglobin, and a promoter of the H(2)O(2)-induced degradation of heme in food vacuoles of the malarial parasite. In this work, we have designed PfHRP2 model peptides, R18 and R27 (18 and 27 residues, respectively), and used them for optical and electron spin resonance spectroscopic measurements to confirm that the axial ligands of the heme-PfHRP2 complex are the nitrogenous donors derived from the imidazole moieties of histidine residues of PfHRP2. In addition, we revealed that the affinities of R18 and R27 for heme (K(d) = 2.21 x 10(-6) M and 0.71 x 10(-6) M, respectively) might be as high as that of PfHRP2 (K(d) = 0.94 x 10(-6) M). The R27 peptide can remove heme from membrane-intercalated heme and inhibit heme-induced hemolysis. Therefore, we suggest another function of PfHRP2: it may play an important role in the neutralization of toxic heme in the parasite cytoplasm and infected erythrocytes by removing heme from heme-bound membranes or reducing heme-induced hemolysis. 相似文献
82.
Kamei H Ding Y Kajimura S Wells M Chiang P Duan C 《Development (Cambridge, England)》2011,138(4):777-786
Animals respond to adverse environments by slowing down or arresting growth and development. Upon returning to normal conditions, they often show compensatory acceleration in growth and developmental rate. This phenomenon, known as `catch-up' growth, is widely documented in the animal kingdom. The underlying molecular mechanisms, however, are poorly understood. Using the zebrafish embryo as an experimental model system, we tested the hypothesis that changes in IGF signaling activities play an important role in the accelerated growth and temporal development resulting from re-oxygenation following hypoxia. We show that chronic hypoxia reduced, and re-oxygenation accelerated, embryonic growth and developmental rate. Whereas hypoxia repressed the Igf1 receptor and its downstream Erk1/2 and Akt signaling activities, re-oxygenation restored their activities. Specific inhibition of Igf1 receptor signaling during re-oxygenation by genetic and pharmacological approaches attenuated catch-up growth. Further analysis showed that whereas PI3K-Akt is required in both normal and catch-up growth, Mek1/2-Erk1/2 activation induced by elevated IGF signaling during re-oxygenation is particularly crucial for catch-up growth. These results suggest that the evolutionarily conserved IGF signaling pathway coordinates growth and temporal development in zebrafish embryos in response to oxygen availability. 相似文献
83.
Shinichiro Muraoka Kenji Kamei Katsumasa Muneoka Morikuni Takigawa 《Journal of neurochemistry》1998,71(4):1709-1718
Abstract: In the present study, we examined whether chronic exposure of C6BU-1 cells to 100 n M of several different types of antidepressants directly influences serotonin2A (5-HT2A ) receptor-stimulated intracellular Ca2+ mobilization. Imipramine, desipramine, clomipramine, and maprotiline amplified the 5-HT response at 48, but not at 2, h. Imipramine increased the maximum response to 5-HT without altering the EC50 of the dose-response curve. This effect was time dependent and cycloheximide blocked the maximal induction, suggesting an essential role for protein synthesis in this process. Previous exposure of the cells to thrombin or isoproterenol did not influence 5-HT2A receptor function and pretreatment with imipramine did not alter the thrombin- or bradykinin-induced Ca2+ mobilization, which indicates that the effects of imipramine appear to be specific to the 5-HT2A receptor. The effect of imipramine was potently suppressed by a calmodulin antagonist, W-13, in a dose-dependent manner. Furthermore, this amplified 5-HT response was blocked by KN-93, but not by H-7. Taken together, these results suggest that imipramine has a modulatory effect on the 5-HT2A receptor-coupled intracellular Ca2+ in C6 cells through a calmodulin-dependent pathway, possibly involving Ca2+ /calmodulin kinase activation. 相似文献
84.
The amino acid sequence of glutathione S-transferase b (GST b) from guinea pig liver was determined by conventional methods. GST b was composed of two identical subunits, each with 217 amino acid residues. As GSTs are generally classified into three classes, alpha, mu, and pi, GST b belonged to class mu and the amino acid sequence of GST b showed about 80% homology with that of rat GST Yb. 相似文献
85.
用FACS分析和Luria-Delbrǔck方程计算淋巴细胞杂交瘤株细胞丧失抗体生成功能的突变机率(μ),以评估杂交瘤的稳定性。结果表明μ值大,则杂交瘤不稳定,易丧失抗体生成功能,反之则杂交瘤比较稳定。实验证明所建立的方法能反映杂交瘤稳定性的程度,具有实验少人为主观因素干扰,统计意义强,适用范围广等优点。 相似文献
86.
α-Galactosidase gene mutations in Fabry disease: heterogeneous expressions of mutant enzyme proteins
Toshika Okumiya Satoshi Ishii Ryoichi Kase Sachiko Kamei Hitoshi Sakuraba Yoshiyuki Suzuki 《Human genetics》1995,95(5):557-561
Five point mutations were identified in unrelated Japanese Fabry disease hemizygotes: three new missense mutations, C142Y (425 G A), A156V (467 C T), and L166V (496 C G) in exon 3; one new splice site mutation at the 3 end of the consensus sequence in exon 4; one previously reported nonsense mutation, W44X (131 G A). C142Y expressed 50% of the normal enzyme protein in COS-1 cells, but catalytic activity was not detected. Both A156V and L166V expressed significant amounts of residual enzyme activity (6.7% and 9.8%) and enzyme proteins (10% each), the latter were more thermolabile at neutral pH than at acid pH, in vitro. 相似文献
87.
It is known thatHistoplasma capsulatum can resist the intraphagolysosomal environment and multiply inside macrophages. This resistance can be closly related to its pathogenicity. The mechanism of this resistance has been investigated, but it has not been clarified as yet. To learn about the metabolic condition of the yeast-form ofH. capsulatum (isolates G217B and CDC 105) when ingested by macrophages, we investigated protein synthesis by ingestedH. capsulatum with [35S]-methionine labeling. Cycloheximide at 5 to 10 µg/ml was used to preferentially inhibit macrophage uptake of [35S]-methionine without affectingH. capsulatum uptake. Protein synthesis byH. capsulatum in medium alone served as a positive control. The negative control consisted of macrophages with ingested heat-killedH. capsulatum. Analysis of cytosols with SDS-PAGE and fluorography disclosed that, respectively for G217B and CDC 105, ingestedH. capsulatum synthesized 4 and 5 novel proteins, increased the synthesis of 9 and 17 proteins and decreased the synthesis of 9 and 10 constitutive proteins. Ten of these novel or increased proteins were apparently common to both strains. These metabolic changes in ingestedH. capsulatum could reflect its adaptation to the intraphagolysosomal environment of macrophages and its ability to multiply there. 相似文献
88.
Hiroaki Kumano Harumi Horie Tomifusa Kuboki Hiroyuki Suematsu Hiroshi Sato Mitsuo Yasushi Tsutomu Kamei Sumio Masumura 《Applied psychophysiology and biofeedback》1997,22(3):193-208
The effect of EEG-driven photic stimulation on stress-related endocrine function was studied. Subjects were 16 healthy males divided into a photic stimulation group (n=8) and a control group (n=8). Electrodermal and emotional lability measures were assessed by nonspecific skin conductance response and the Maudsley Personality Inventory, respectively. Plasma cortisol and -endorphin concentrations were measured both before and after EEG-driven photic stimulation as well as the resting condition. Subjects with electrodermal, emotional, or both lability showed comparable decreases of plasma -endorphin on photic stimulation as did the stable subjects. Under resting control conditions, however, they showed significant increases of -endorphin compared to both stable subjects as well as the photic stimulation condition. In addition, labile subjects showed significant alpha enhancement on photic stimulation compared to stable subjects and to the resting control condition. The data suggest that increases of plasma -endorphin in labile control subjects may denote a stress response to the conditions of these experiments, and that any decrease by EEG-driven photic stimulation may indicate a reduction of responsiveness to an acute stress. 相似文献
89.
90.