全文获取类型
收费全文 | 977篇 |
免费 | 103篇 |
出版年
2022年 | 5篇 |
2018年 | 6篇 |
2017年 | 12篇 |
2016年 | 7篇 |
2015年 | 27篇 |
2014年 | 34篇 |
2013年 | 50篇 |
2012年 | 46篇 |
2011年 | 47篇 |
2010年 | 23篇 |
2009年 | 20篇 |
2008年 | 39篇 |
2007年 | 37篇 |
2006年 | 34篇 |
2005年 | 35篇 |
2004年 | 46篇 |
2003年 | 50篇 |
2002年 | 55篇 |
2001年 | 37篇 |
2000年 | 41篇 |
1999年 | 33篇 |
1998年 | 18篇 |
1997年 | 23篇 |
1996年 | 23篇 |
1995年 | 14篇 |
1994年 | 16篇 |
1993年 | 13篇 |
1992年 | 27篇 |
1991年 | 19篇 |
1990年 | 17篇 |
1989年 | 20篇 |
1988年 | 29篇 |
1987年 | 20篇 |
1986年 | 5篇 |
1985年 | 11篇 |
1984年 | 15篇 |
1983年 | 6篇 |
1982年 | 11篇 |
1981年 | 8篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 11篇 |
1977年 | 9篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1973年 | 4篇 |
1968年 | 5篇 |
1967年 | 10篇 |
1966年 | 8篇 |
1965年 | 5篇 |
排序方式: 共有1080条查询结果,搜索用时 500 毫秒
971.
Okazaki K Amano T Morimoto T Iemoto T Kawabata T Hayakawa S Akimitsu K 《Bioscience, biotechnology, and biochemistry》2001,65(7):1684-1687
Mycodextranase (EC 3.2.1.61) is an alpha-glucanase that cleaves alpha-1,4-bonds of alternating alpha-1,3- and alpha-1,4-linked D-glucan (nigeran). The gene encoding mycodextranase from Streptomyces sp. J-13-3 was cloned by hybridization with a degenerate oligonucleotide probe from the amino-terminal amino acid sequence of the enzyme and its nucleotide structure was analyzed. The open reading frame consisted of 1,803 base pairs encoding a signal peptide of 60 amino acids and a mature protein of 540 amino acids with a calculated molecular weight of 56,078. The deduced amino acid sequence showed weak similality to a chitinase homolog from Streptomyces lividans and a chitinase from Xanthomonas sp. 相似文献
972.
Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia 总被引:10,自引:0,他引:10
Yagyu H Kitamine T Osuga J Tozawa R Chen Z Kaji Y Oka T Perrey S Tamura Y Ohashi K Okazaki H Yahagi N Shionoiri F Iizuka Y Harada K Shimano H Yamashita H Gotoda T Yamada N Ishibashi S 《The Journal of biological chemistry》2000,275(28):21324-21330
Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes esterification of cellular cholesterol. To investigate the role of ACAT-1 in atherosclerosis, we have generated ACAT-1 null (ACAT-1-/-) mice. ACAT activities were present in the liver and intestine but were completely absent in adrenal, testes, ovaries, and peritoneal macrophages in our ACAT-1-/- mice. The ACAT-1-/- mice had decreased openings of the eyes because of atrophy of the meibomian glands, a modified form of sebaceous glands normally expressing high ACAT activities. This phenotype is similar to dry eye syndrome in humans. To determine the role of ACAT-1 in atherogenesis, we crossed the ACAT-1-/- mice with mice lacking apolipoprotein (apo) E or the low density lipoprotein receptor (LDLR), hyperlipidemic models susceptible to atherosclerosis. High fat feeding resulted in extensive cutaneous xanthomatosis with loss of hair in both ACAT-1-/-:apo E-/- and ACAT-1-/-:LDLR-/- mice. Free cholesterol content was significantly increased in their skin. Aortic fatty streak lesion size as well as cholesteryl ester content were moderately reduced in both double mutant mice compared with their respective controls. These results indicate that the local inhibition of ACAT activity in tissue macrophages is protective against cholesteryl ester accumulation but causes cutaneous xanthomatosis in mice that lack apo E or LDLR. 相似文献
973.
974.
Apolipoprotein-mediated cellular cholesterol/phospholipid efflux and plasma high density lipoprotein level in mice 总被引:2,自引:0,他引:2
Tsujita M Tomimoto S Okumura-Noji K Okazaki M Yokoyama S 《Biochimica et biophysica acta》2000,1485(2-3):199-213
Helical apolipoprotein(apo)s generate pre-beta-high density lipoprotein (HDL) by removing cellular cholesterol and phospholipid upon the interaction with cells. To investigate its physiological relevance, we studied the effect of an in vitro inhibitor of this reaction, probucol, in mice on the cell-apo interaction and plasma HDL levels. Plasma HDL severely dropped in a few days with probucol-containing chow while low density protein decreased more mildly over a few weeks. The peritoneal macrophages were assayed for apoA-I binding, apoA-I-mediated release of cellular cholesterol and phospholipid and the reduction by apoA-I of the ACAT-available intracellular cholesterol pool. All of these parameters were strongly suppressed in the probucol-fed mice. In contrast, the mRNA levels of the potential regulatory proteins of the HDL level such as apoA-I, apoE, LCAT, PLTP, SRB1 and ABC1 did not change with probucol. The fractional clearance rate of plasma HDL-cholesteryl ester was uninfluenced by probucol, but that of the HDL-apoprotein was slightly increased. No measurable CETP activity was detected either in the control or probucol-fed mice plasma. The change in these functional parameters is consistent with that observed in the Tangier disease patients. We thus concluded that generation of HDL by apo-cell interaction is a major source of plasma HDL in mice. 相似文献
975.
976.
Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The N-terminal alpha-helix domain of the human immunodeficiency virus type 1 (HIV-1) Nef protein plays important roles in enhancement of viral infectivity, virion incorporation of Nef, and the down-regulation of major histocompatibility complex class I (MHC-I) expression on cell surfaces. In this study, we demonstrated that Met 20 in the alpha-helix domain was indispensable for the ability of Nef to modulate MHC-I expression but not for other events. We also showed that Met 20 was unnecessary for the down-regulation of CD4. These findings indicate that the region governing MHC-I down-regulation is proximate in the alpha-helix domain but is dissociated functionally from that determining enhancement of viral infectivity, virion incorporation of Nef, and CD4 down-regulation. 相似文献
977.
Okumura-Noji K Sasai K Zhan R Kawaguchi H Maruyama H Tada T Takahashi H Okazaki M Miida T Sakuma N Kimura G Ohta N Yokoyama S 《Biochemical and biophysical research communications》2001,281(2):305-310
It was investigated whether proteasome activity was implicated in susceptibility of human vascular smooth muscle cells (VSMCs) to Fas-mediated death. Human fetal aorta smooth muscle cells were treated with agonistic anti-Fas antibody (CH11) and proteasome inhibitors (MG115 or MG132) and then cell death was determined by morphology, viability, and DNA fragmentation. The present study reports that: (a) crosslinking of Fas receptor with anti-Fas antibody in the presence of proteasome inhibitor-induced death and DNA degradation in human VSMCs that were blocked by caspases inhibitor z-DEVD.fmk; (b) cotreatment with anti-Fas antibody and proteasome inhibitor activated caspase-3; (c) proteasome inhibitors did not influence expression of procaspase-8, procaspase-3, c-FLIP, and Bcl-2; and (d) proteasome inhibitors up-regulated Fas and FADD. The data indicate that proteasome activity is important in survival of VSMCs and provide the first evidence that proteasome is involved in Fas signal transduction. The present study proposes novel mechanism(s) by which VSMCs become susceptible to FasL. 相似文献
978.
Serotonin and dopamine are involved in the attachment and metamorphosis of cypris larvae of barnacles. Aromatic L-amino acid decarboxylase (AADC) gene, the product of which catalyzes the synthesis of serotonin and dopamine from L-5-hydroxytryptophan and L-3,4-dihydroxyphenylalanine, respectively, was characterized. A DNA clone containing part of an AADC sequence was obtained from the genomic DNA library of the barnacle, Balanus amphitrite. This clone had four putative exons consisting of 226 amino acids with an identity of 63.2% and a similarity of 92.1% with human AADC. Northern blot analysis showed that AADC mRNA was expressed at all stages of barnacles: naupliar larvae, cypris larvae and adult barnacles. Two inducers of larval attachment and metamorphosis; that is, serotonin and extract of adult barnacles, obviously increased the expression of AADC mRNA at an early cypris larval stage. These results suggest that intracellular biosynthesis of serotonin, or dopamine, or both is at least partly involved in the control of the attachment and metamorphosis of cypris larvae. 相似文献
979.
Lipase-catalyzed optical resolution of (+/-)-epoxy-beta-cyclogeraniol (1), a key synthetic intermediate for epoxy-beta-ionylideneacetic acid, was achieved in high enantiomeric purity. Transesterification with vinyl acetate by using lipase P (Nagase) made enriched (-)-1, while hydrolysis of the corresponding acetate by using lipase P (Amano) afforded (+)-1 with a high E value (E = 1600). 相似文献
980.
Fujita Y Yanagida H Mimori T Jin ZX Sakai T Kawanami T Sawaki T Masaki Y Fukushima T Okazaki T Umehara H 《Cellular immunology》2012,273(1):52-58
Leptin is an adipokine that regulates body weight. In the current study, we demonstrate that continuous injection of leptin prevents the lymphocyte reduction observed in fasted mice, especially the immature B cell populations in the bone marrow. Although leptin administration reduced apoptotic cells in the bone marrow of fasted mice, it did not prevent glucocorticoid-mediated apoptosis in vitro. Bone marrow atrophy has also been shown in the leptin receptor-deficient db/db mice. In order to investigate the mechanisms underlying these processes, we transplanted bone marrow cells from db/db or control (+m/+m) mice into C.B-17/lcr-scid/scid mice. We found that the spleen and bone marrow B cell populations were completely reconstituted when db/db and +m/+m cells were transplanted into scid mice. Our findings suggest that direct interactions between leptin and bone marrow cells are not essential for the development of B cells in a metabologically normal environment. 相似文献