全文获取类型
收费全文 | 4831篇 |
免费 | 307篇 |
国内免费 | 1篇 |
出版年
2022年 | 26篇 |
2021年 | 52篇 |
2020年 | 24篇 |
2019年 | 42篇 |
2018年 | 58篇 |
2017年 | 49篇 |
2016年 | 86篇 |
2015年 | 161篇 |
2014年 | 186篇 |
2013年 | 300篇 |
2012年 | 259篇 |
2011年 | 261篇 |
2010年 | 174篇 |
2009年 | 181篇 |
2008年 | 264篇 |
2007年 | 276篇 |
2006年 | 278篇 |
2005年 | 283篇 |
2004年 | 297篇 |
2003年 | 273篇 |
2002年 | 256篇 |
2001年 | 125篇 |
2000年 | 120篇 |
1999年 | 123篇 |
1998年 | 72篇 |
1997年 | 54篇 |
1996年 | 45篇 |
1995年 | 39篇 |
1994年 | 45篇 |
1993年 | 41篇 |
1992年 | 86篇 |
1991年 | 40篇 |
1990年 | 57篇 |
1989年 | 42篇 |
1988年 | 68篇 |
1987年 | 33篇 |
1986年 | 34篇 |
1985年 | 29篇 |
1984年 | 20篇 |
1983年 | 28篇 |
1982年 | 32篇 |
1981年 | 32篇 |
1980年 | 13篇 |
1979年 | 25篇 |
1978年 | 18篇 |
1977年 | 14篇 |
1976年 | 13篇 |
1975年 | 13篇 |
1974年 | 13篇 |
1973年 | 20篇 |
排序方式: 共有5139条查询结果,搜索用时 15 毫秒
71.
Purified rat brain Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) is stimulated by brain gangliosides to a level of about 30% the activity obtained in the presence of Ca2+/calmodulin (CaM). Of the various gangliosides tested, GT1b was the most potent, giving half-maximal activation at 25 microM. Gangliosides GD1a and GM1 also gave activation, but asialo-GM1 was without effect. Activation was rapid and did not require calcium. The same gangliosides also stimulated the autophosphorylation of CaM-kinase II on serine residues, but did not produce the Ca2+-independent form of the kinase. Ganglioside stimulation of CaM-kinase II was also present in rat brain synaptic membrane fractions. Higher concentrations (125-250 microM) of GT1b, GD1a, and GM1 also inhibited CaM-kinase II activity. This inhibition appears to be substrate-directed, as the extent of inhibition is very dependent on the substrate used. The molecular mechanism of the stimulatory effect of gangliosides was further investigated using a synthetic peptide (CaMK 281-309), which contains the CaM-binding, inhibitory, and autophosphorylation domains of CaM-kinase II. Using purified brain CaM-kinase II in which these regulatory domains were removed by limited proteolysis. CaMK 281-309 strongly inhibited kinase activity (IC50 = 0.2 microM). GT1b completely reversed this inhibition, but did not stimulate phosphorylation of the peptide on threonine-286. These results demonstrate that GT1b can partially mimic the effects of Ca2+/CaM on native CaM-kinase II and on peptide CaMK 281-309. 相似文献
72.
Membrane Viscosity Correlates with α1 -Adrenergic Signal Transduction of the Aged Rat Cerebral Cortex
Atsushi Miyamoto Tsunehisa Araiso Tomiyasu Koyama Hideyo Ohshika 《Journal of neurochemistry》1990,55(1):70-75
We investigated, using adult (2-month-old) and senescent (12- and 24-month-old) rats, the effects of aging on the relationship between the alpha 1-adrenergic coupling system and the membrane viscosity of the cerebral cortex. There was no age-related difference in the KD values of [3H]prazosin binding on the membranes. The Bmax values of [3H]prazosin binding were reduced with advanced age. Norepinephrine-induced formation of 3H-labeled inositol phosphates (3H-IPs) in the slices increased with advanced age. The EC50 values for norepinephrine to stimulate the formation of 3H-IPs at advanced age were lower than that at adult age. The cholesterol content in membranes increased with advanced age. No changes in the phospholipid content in membranes were observed with advanced age. Concomitantly, an increase of the molar ratio of cholesterol to phospholipids was observed with advanced age. The membrane viscosity as measured by 1,6-diphenyl-1,3,5-hexatriene increased with advanced age. These results indicate that the altered cholesterol content and/or viscosity in cortical membranes of the aged rat may account for the loss of alpha 1-adrenergic receptor density and/or compensatory changes in the receptor-phospholipase C coupling system. 相似文献
73.
Nakazawa Miki; Kakihana Junko; Hisabori Toru; Manabe Katsushi 《Plant & cell physiology》1990,31(6):789-796
Procedures for the purification of native phytochrome from etiolatedpea seedlings without the use of immuno-purification techniquesare described. Phytochrome (in the PFR form) was purified bypolyethyleneglycol fractionation, adsorption to pentyl agaroseand batch elution, chromatography on DEAE-Sepharose, adsorptionto phenyl Toyopearl and batch elution, and chromatography onRed Toyopearl. The resulting phytochrome had specific absorbanceratios (SAR = A666/A280 of PR) that ranged from 0.55 to 0.6.The subsequent chromatography on Sephacryl S-300 yielded verypure phytochrome with a SAR of 0.98. PR and PFR peaks in thedifference spectrum of the phytochrome were centered at 665and 730 nm, respectively. The spectral change ratio (Ar/Afr)of the difference spectrum was unchanged after the chromatographyon phenyl Toyopearl, and the value was 1.051.08, indicatingthat the spectral properties of this preparation were intact.The absorption spectra indicated that the peak absorbance ofPFR was at 728730 nm and that of PR was at 666667nm. These peak positions were essentially same as those obtainedwith the undegraded oat phytochrome. Incubation of the samplepurified on Sephacryl S-300 at 25?C for 5 h in either the PRor PFR form did not result in degradation of the molecule. Therate of dark reversion of PFR observed with the purified peaphytochrome was similar to that observed in vivo. The additionof dithionite had no effect on the reversion rate.
2Present address: Fuji-Gotenba, Research Lab. of Chugai PharmaceuticalCo. Ltd., Gotenba, Shizuoka, 412 Japan (Received February 22, 1990; Accepted May 28, 1990) 相似文献
74.
75.
T Oka M K Thakur K Miyamoto T Sassa I Suzuki Y Natori 《Biochemical and biophysical research communications》1992,189(1):179-183
The degradation of H1 histone and high mobility group (HMG) nonhistone proteins was stimulated when the homogenate from chick liver was incubated in the presence of phenylmethylsulfonyl fluoride (PMSF). Two proteinase inhibitors, elastatinal and chymostatin, significantly inhibited the PMSF-stimulated degradation of H1 histone and HMG proteins. On the contrary, other proteinase inhibitors like leupeptin, pepstatin, trypsin inhibitor, antipain, o-phenanthroline and EDTA had no effect on the degradation of the nuclear proteins. These results warn the researcher to be cautious while using PMSF for preparation of nuclear proteins such as H1 histone and HMG proteins. 相似文献
76.
K Ueno T Katayama T Miyamoto Y Koshihara 《Biochemical and biophysical research communications》1992,189(3):1521-1526
The effect of human interleukin-4 (hIL-4) on mineralization in human osteoblast-like cells was investigated. Confluent cells were incubated with hIL-4 for 16 or 30 days in the presence or absence, respectively, of alpha-glycerophosphate (alpha-GP), which accelerates the mineralization process. hIL-4 (0.3 ng/ml) induced mineralization with 1.9-, 26- and 37-fold increases of hydroxyproline, calcium, and osteocalcin content, respectively, in the presence of alpha-GP. Mineralization was not induced with other cytokines, hIL-1, hIL-2, hIL-6, or mIL-4. hIL-4 also induced mineralization in the absence of alpha-GP in a manner different from that of 1 alpha, 25(OH)2 vitaminD3 (1,25(OH)2VD3). These findings suggest that IL-4 may play an important role in bone formation. 相似文献
77.
Y Ohyama K Miyamoto Y Saito N Minamino K Kangawa H Matsuo 《Biochemical and biophysical research communications》1992,183(2):743-749
Two similar membrane bound guanylate cyclases (GC-A and GC-B) are known as natriuretic peptide receptors, but have not been well characterized yet. In this study, we have isolated two forms of GC-B cDNA clones along with GC-A cDNA clones from rat brain. The two forms of rat GC-B differ from each other only by 75bp deletion at 3'-flanking region of the putative transmembrane domain, the shorter form lacking the nucleotide binding site by the deletion. Expression of these cDNAs on mammalian cells revealed that (1) GC-B is a specific receptor for CNP whereas GC-A is stimulated effectively both by ANP and BNP, and (2) the two forms of GC-B possess practically the same high binding affinity for CNP while the shorter form could not induce cGMP production by the binding of CNP. These data indicate that in rat brain is present the non-functional receptor for CNP caused by the short deletion. 相似文献
78.
H Nishio H Matsui L J Moia S Taketa K Miyamoto M Tokuda T Itano S Nakahara O Hatase 《Biochemical and biophysical research communications》1992,187(2):828-831
The expression of a regulatory subunit of calcineurin (CaN beta) during rat spermatogenesis was examined in rat testes using a monoclonal antibody Va1. Results showed that a testis-specific isoform of CaN beta was expressed only 3 weeks after birth, when meiosis begins, and increased in amount depending on the maturation of spermatogenesis. The matured sperm, which consists of only post-meiotic cells, is most likely to have only the testis-specific isoform of CaN beta. The brain type isoform of CaN beta was not detected in rat sperm. Immunoblot analysis of testes from different rodent species by a monoclonal antibody Va1 showed that all rodent species examined had their own homologues corresponding to a testis-specific isoform of CaN beta in rats, although they showed distinctively different molecular weights on SDS-PAGE compared to the testis-specific isoform in rats. Each homologue was shown to be specifically expressed in post-meiotic phase of spermatogenesis, as was seen in rats. 相似文献
79.
K Miyamoto K Hase Y Taketani H Minami T Oka Y Nakabou H Hagihira 《Biochemical and biophysical research communications》1992,183(2):626-631
Developmental changes in glucose transporter mRNA levels in the jejunum of rats of different ages were examined by using slot blot RNA analysis. The level of SGLT1 mRNA did not change significantly through life. The GLUT5 mRNA level was highest in 10-day-old rats and then decreased reaching the adult level by day 20 after birth. The GLUT2 mRNA level was low in rats of 5 and 10 days old, but then increased progressively reaching the adult value by day 25 after birth. These results indicate that the expressions of intestinal facilitative glucose transporter genes change markedly in the third week after birth. 相似文献