全文获取类型
收费全文 | 358篇 |
免费 | 16篇 |
国内免费 | 2篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 9篇 |
2014年 | 17篇 |
2013年 | 40篇 |
2012年 | 24篇 |
2011年 | 21篇 |
2010年 | 10篇 |
2009年 | 5篇 |
2008年 | 13篇 |
2007年 | 25篇 |
2006年 | 24篇 |
2005年 | 14篇 |
2004年 | 23篇 |
2003年 | 15篇 |
2002年 | 23篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 9篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有376条查询结果,搜索用时 15 毫秒
91.
The B820 subunit is an integral pigment-membrane protein complex and can be obtained by both dissociation of the core light-harvesting complex (LH1) in photosynthetic bacteria and reconstitution from its component parts in the presence of n-octyl beta-D-glucopyranoside (OG). Intrinsic size of the B820 subunit from Rhodospirillum rubrum LH1 complex was measured by small-angle neutron scattering in perdeuterated OG solution and evaluated by Guinier analysis. Both the B820 subunits prepared by dissociation of LH1 and reconstitution from apopolypeptides and pigments were shown to have a molecular weight of 11,400 +/- 500 and radius of gyration of 11.0 +/- 1.0 A, corresponding to a heterodimer consisting of one pair of alphabeta-polypeptides and two bacteriochlorophyll a molecules. Molecular weights of micelles formed by OG alone in solutions were determined in a range from 30,000 to 50,000 over concentrations of 1-5% (w/v), and thus are much larger than that of the B820 subunit. Similar measurement on the pigment-depleted apopolypeptides revealed highly heterogeneous behavior in the OG solutions, indicating that aggregates with various sizes were formed. The result provides evidence that bacteriochlorophyll a molecules play a crucial role in stabilizing and maintaining the B820 subunits in the dimeric state in solution. Further measurements on individual alpha- and beta-polypeptides exhibited a marked difference in aggregation property between the two polypeptides. The alpha-polypeptides appear to be uniformly dissolved in OG solution in a monomeric form, whereas the beta-polypeptides favor a self-associated form and tend to form large aggregates even in the presence of detergent. The difference in aggregation tendency was discussed in relation to the different behavior between alpha- and beta-polypeptides in reconstitution with bacteriochlorophyll a molecules. 相似文献
92.
Modulation of cardiac sodium channel gating by protein kinase A can be altered by disease-linked mutation 总被引:3,自引:0,他引:3
Tateyama M Rivolta I Clancy CE Kass RS 《The Journal of biological chemistry》2003,278(47):46718-46726
Mutations associated with sodium channel-linked inherited Long-QT syndrome often result in a gain of channel function by disrupting channel inactivation. A small fraction of channels fail to inactivate (burst) at depolarized potentials where normal (wild type) channels fully inactivate. These noninactivating channels give rise to a sustained macroscopic current. We studied the effects of protein kinase A stimulation on sustained current in wild type and three disease-linked C-terminal mutant channels (D1790G, Y1795C, and Y1795H). We show that protein kinase A stimulation differentially affects gating in the mutant channels. Wild type, Y1795C, and Y1795H channels are insensitive to protein kinase A stimulation, whereas "bursting" in the D1790G mutant is markedly enhanced by protein kinase A-dependent phosphorylation. Our results suggest that the charge at position 1790 of the C terminus of the channel modulates the response of the cardiac sodium channel to protein kinase A stimulation and that phosphorylation of residue 36 in the N terminus and residue 525 in the cytoplasmic linker joining domains I and II of the channel alpha subunit facilitate destabilization of inactivation and thereby increase sustained current. 相似文献
93.
It has been reported that concentrations of neopterin in the urine are changed according to the host immunological conditions. In the present study, we measured urinary concentration of neopterin in patients with malignant hematological disorders and investigated the relationship between urinary neopterin levels and laboratory indices for cellular immunity. Urine neopterin levels were correlated with serum sIL-2R levels in the patients with malignant lymphoma, and inversely correlated with lymphocyte reactivity with ConA in the patients with acute myelocytic leukemia. However, no significant correlation was observed between urine neopterin levels and lymphocyte reactivity with phytohemagglutinin and pokeweed mitogen, CD4/8 ratio, CD56+ 16+ subset or serum IFN-gamma levels. In the patients with malignant lymphoma, parallel changes in serum sIL-2R and urine neopterin were observed. The presented results suggest that urine neopterin levels are related to the activation of T cells in malignant lymphoma. 相似文献
94.
Requirement for Activation of the Serine-Threonine Kinase Akt (Protein Kinase B) in Insulin Stimulation of Protein Synthesis but Not of Glucose Transport 总被引:17,自引:6,他引:11 下载免费PDF全文
Tadahiro Kitamura Wataru Ogawa Hiroshi Sakaue Yasuhisa Hino Shoji Kuroda Masafumi Takata Michihiro Matsumoto Tetsuo Maeda Hiroaki Konishi Ushio Kikkawa Masato Kasuga 《Molecular and cellular biology》1998,18(7):3708-3717
A wide variety of biological activities including the major metabolic actions of insulin is regulated by phosphatidylinositol (PI) 3-kinase. However, the downstream effectors of the various signaling pathways that emanate from PI 3-kinase remain unclear. Akt (protein kinase B), a serine-threonine kinase with a pleckstrin homology domain, is thought to be one such downstream effector. A mutant Akt (Akt-AA) in which the phosphorylation sites (Thr308 and Ser473) targeted by growth factors are replaced by alanine has now been shown to lack protein kinase activity and, when overexpressed in CHO cells or 3T3-L1 adipocytes with the use of an adenovirus vector, to inhibit insulin-induced activation of endogenous Akt. Akt-AA thus acts in a dominant negative manner in intact cells. Insulin-stimulated protein synthesis, which is sensitive to wortmannin, a pharmacological inhibitor of PI 3-kinase, was abolished by overexpression of Akt-AA without an effect on amino acid transport into the cells, suggesting that Akt is required for insulin-stimulated protein synthesis. Insulin activation of p70 S6 kinase was inhibited by ~75% in CHO cells and ~30% in 3T3-L1 adipocytes, whereas insulin-induced activation of endogenous Akt was inhibited by 80 to 95%, by expression of Akt-AA. Thus, Akt activity appears to be required, at least in part, for insulin stimulation of p70 S6 kinase. However, insulin-stimulated glucose uptake in both CHO cells and 3T3-L1 adipocytes was not affected by overexpression of Akt-AA, suggesting that Akt is not required for this effect of insulin. These data indicate that Akt acts as a downstream effector in some, but not all, of the signaling pathways downstream of PI 3-kinase. 相似文献
95.
A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese 总被引:42,自引:0,他引:42
Michihiro Yoshimura H. Yasue Masafumi Nakayama Yukio Shimasaki Hitoshi Sumida Seigo Sugiyama Kiyotaka Kugiyama Hisao Ogawa Yoshihiro Ogawa Yoshihiko Saito Yoshihiro Miyamoto Kazuwa Nakao 《Human genetics》1998,103(1):65-69
Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in
general. However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm may arise
from interactions between environmental and genetic factors. Endothelial derived nitric oxide (NO) has been implicated in
the control of vascular tone. We have recently shown that both basal and acetylcholine (ACh)-induced NO activities are impaired
in the coronary arteries of patients with coronary spasm. The purpose of this study has been to elucidate the possible variants
that occur in the coding region of the endothelial nitric oxide synthase (eNOS) gene and that may be associated with coronary
spasm. After initial screening in the entire 26 coding regions of the eNOS gene, we found a missense Glu298Asp variant in
exon 7 in patients with coronary spasm. We subsequently performed a larger scale study involving 113 patients with coronary
spasm and 100 control subjects, who were all diagnosed by intracoronary injection of ACh. The analysis revealed a significant
difference in the distribution of the variant between the coronary spasm group (21.2%) and control group (9.0%; P=0.014 for dominant effect). Thus, we have found the missense Glu298Asp variant in the eNOS gene by the analysis of its entire
26 coding regions. The variant is significantly associated with coronary spasm.
Received: 2 February 1998 / Accepted: 9 April 1998 相似文献
96.
Shinsuke Umeda Radha Ayyagari Michihiro T Suzuki Fumiko Ono Fumino Iwata Keiko Fujiki Atsushi Kanai Yuichiro Takada Yasuhiro Yoshikawa Yasuhiko Tanaka Takeshi Iwata 《Experimental Animals》2003,52(2):129-135
ELOVL4, elongation factor of very long chain fatty acids-4, is known to be responsible for autosomal dominant macular degeneration and Stargardt-like macular degeneration. In this study, we cloned the monkey homologue of ELOVL4 and determined the cellular and tissue distribution of the gene product. Sequence analysis of the monkey ELOVL4 gene revealed a high degree of homology between human and monkey. The cloned full-length cDNA of monkey ELOVL4 encoded 314 amino acids, the same length as human and two amino acids longer than mouse. The monkey ELOVL4 conserved the characteristics typical of the super family of ELO enzymes involved in the metabolism of membrane-bound fatty acid elongation. Real-time quantitative PCR demonstrated that the monkey ELOVL4 gene was highly expressed in restricted tissue-specific fashion, not only in the retina but also in the skin (90% of retina) and thymus (111% of retina). Immunohistochemical analysis detected signals predominantly in the photoreceptor layer of the monkey retina. 相似文献
97.
Toshiyuki Kitajima Michihiro Iwashiro Kagemasa Kuribayashi Sadao Imamura 《Cancer immunology, immunotherapy : CII》1994,38(6):372-378
Six ultraviolet-light(UV)-induced tumors of (BALB/c×C57BL/6)F1 (H-2d/b) mouse origin were analyzed for the effector T cell subsets involved in tumor rejection the MHC class I to which cytolytic T lymphocytes (CTL) are restricted, and the effect of UV radiation on tumor rejection, to characterize their tumor-rejection antigens (TRA) recognized by CTL. All tumors were rejected in syngeneic normal mice but grew progressively in nude mice. CD8+ T cells mediated the antitumor responses for all tumors and CD4+ T cells could also do so for one tumor 6.1B. Each tumor induced potent CTL that recognized the specific TRA in preferential association with MHC class I haplotypes not from H-2b but from H-2d; that is, Kd, Dd or Ld. Profiles of TRA expression on two tumors were obtained by the analyses of their antigen-loss variants. 1A codominantly expressed at least four distinct TRA associated with Kd, all of which induced CTL. On the other hand, UV 1 had at least two distinct TRA, one of which, associated with Kd, exclusively induced CTL. However, in the absence of the dominant TRA, another TRA associated with Ld on R95C, a variant of UV, 1, induced CTL. Unlike other tumors, R95C grew progressively in short-term-UV-irradiated syngeneic mice. Nude mice reconstituted with a combination of CD4+ T cells from short-term-UV-irradiated mice and CD8+ T cells from normal mice did not reject R95C. An increase in the former T cell population led the reconstituted mice to reject the tumor. These findings suggest some functional defects of CD4+ T cells rather than the generation of suppressor cells in short-term-UV-irradiated mice. The UV-induced tumors used in the present study provide a unique system for analyzing the preferential sorting of TRA as well as for elucidation of the TRA itself. 相似文献
98.
Naoki Sugawara Dan Li Michihiro Katakura Chieko Sugawara 《Biological trace element research》1994,46(1-2):125-134
Increased biliary Cu excretion was found in Fischer rats injected with Cu. The biliary Cu was located at the void (large-molecule region) and total (small-molecule region) volume of a Sephadex G-75 column. The most Cu was found in the total volume. The two Cu peaks comigrated with absorbance at 280 nm. Although the bile from Cu-untreated Fischer rats did not show Cu absorbance in the total volume, absorbance at 280 nm was also found in this region. Even though Long-Evans Cinnamon (LEC) rats deposited a gross amount of Cu (194.0±27.8 μg/g liver) in the liver, they conversely showed reduced Cu excretion into the bile. LEC bile did not show Cu absorbance but rather absorbance at 280 nm in the total volume. Therefore, it seems unlikely that the small molecules found in the Sephadex G-75 regulate biliary Cu excretion in Cu-loaded rats, although the molecules bind to Cu. When the bile from Cu-untreated fischer and LEC rats was incubated with CuCl2 solution, the most Cu was recovered in the total volume of this column. Our results suggest that reduced biliary Cu excretion in LEC rats is not related to the small molecules, and that Cu cannot be excreted in the form of macromolecules in rats to decrease Cu from the Cu-loaded liver. 相似文献
99.
用1例日本滑膜肉瘤(SS)患者的瘤组织标本接种裸鼠,获得了肿瘤生长。亲本肿瘤与裸鼠肿瘤在病理组织形态上存在一定差异,但两者的免疫组织化学特征相同。染色体分析表明,SS细胞株存在染色体数目和结构异常,患者外周血淋巴细胞染色体核型为正常女性,46,XX。 SS细胞株巴氏小体检出率低于对照,其正常X染色体比易位X染色体晚复制17小时。DNA印迹实验表明,SS DNA存在D2S3座位等位片段丢失,D1S57,D17S5和D13S30座位基因的部分缺失,但无DXS7,DXS14,和D2S44座位基因改变。 相似文献
100.
(1) Mixed bile salt micelle solubilized either cholesterol or β-sitosterol to a comparable extent. When added simultaneously, β-sitosterol restricted the micellar solubility of cholesterol. (2) β-Sitosterol also reduced the cholesterol content in the aqueous (micellar) phase of the intestinal contents of rats, the extent of reduction being comparable with that observed in vitro. The intestinal uptake of cholesterol in vivo was equivalent to the micellar incorporation of cholesterol both in vitro and in vivo. (3) β-Sitosterol had no inhibitory effect on cholesterol absorption from the micellar solution in jejunal loops in situ, whereas the rate of β-sitosterol uptake was only about one-fifth that of cholesterol. (4) The intestinal uptake of β-sitosterol intubated into the stomach of rats was about one-fifth that of cholesterol. The intestinal brush-border membrane discriminated these sterols. These results suggest that the restriction of the micellar solubility of cholesterol, rather than the inhibition of uptake from brush-border membrane, is the major determinant for the interference of β-sitosterol with cholesterol absorption. 相似文献