全文获取类型
收费全文 | 2018篇 |
免费 | 103篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 30篇 |
2020年 | 10篇 |
2019年 | 10篇 |
2018年 | 37篇 |
2017年 | 17篇 |
2016年 | 29篇 |
2015年 | 57篇 |
2014年 | 63篇 |
2013年 | 119篇 |
2012年 | 123篇 |
2011年 | 129篇 |
2010年 | 80篇 |
2009年 | 65篇 |
2008年 | 100篇 |
2007年 | 135篇 |
2006年 | 99篇 |
2005年 | 103篇 |
2004年 | 125篇 |
2003年 | 116篇 |
2002年 | 129篇 |
2001年 | 45篇 |
2000年 | 44篇 |
1999年 | 28篇 |
1998年 | 20篇 |
1997年 | 37篇 |
1996年 | 20篇 |
1995年 | 25篇 |
1994年 | 21篇 |
1993年 | 25篇 |
1992年 | 24篇 |
1991年 | 24篇 |
1990年 | 21篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 13篇 |
1986年 | 17篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 9篇 |
1982年 | 14篇 |
1981年 | 20篇 |
1980年 | 20篇 |
1979年 | 10篇 |
1978年 | 9篇 |
1977年 | 11篇 |
1976年 | 6篇 |
1975年 | 5篇 |
1974年 | 8篇 |
排序方式: 共有2121条查询结果,搜索用时 15 毫秒
121.
Syntheses and biological evaluation of novel quinuclidine derivatives as squalene synthase inhibitors 总被引:2,自引:0,他引:2
Ishihara T Kakuta H Moritani H Ugawa T Sakamoto S Tsukamoto S Yanagisawa I 《Bioorganic & medicinal chemistry》2003,11(11):2403-2414
Squalene synthase (E.C. 2.5.1.21) catalyses the reductive dimerization of two molecules of farnesyl diphosphate to form squalene and is involved in the first committed step in cholesterol biosynthesis. Inhibition of this enzyme is therefore an attractive target for hypocholesterolemic strategies. A series of quinuclidine derivatives incorporating a tricyclic system was synthesized and evaluated for their ability to inhibit squalene synthase in vitro. A 9H-fluorene moiety was found to be optimal as the tricyclic system for potent inhibitory activity. Improved activity can be achieved with a conformationally constrained three-atom linkage connecting the tricyclic system with the quinuclidine nucleus. Among these compounds, (Z)-3-[2-(9H-fluoren-2-yloxy)ethylidene]-quinuclidine hydrochloride 31 was found to be a potent inhibitor of squalene synthase derived from hamster liver and human hepatoma cells with IC(50) values of 76 and 48 nM, respectively. Oral dosing of compound 31 demonstrated effective reduction of plasma non-HDL cholesterol levels in hamsters. 相似文献
122.
123.
We investigated the contribution of the Na(+)/L-carnitine cotransporter in the transport of tetraethylammonium (TEA) by rat renal brush-border membrane vesicles. The transient uphill transport of L-carnitine was observed in the presence of a Na(+) gradient. The uptake of L-carnitine was of high affinity (K(m)=21 microM) and pH dependent. Various compounds such as TEA, cephaloridine, and p-chloromercuribenzene sulfonate (PCMBS) had potent inhibitory effects for L-carnitine uptake. Therefore, we confirmed the Na(+)/L-carnitine cotransport activity in rat renal brush-border membranes. Levofloxacin and PCMBS showed different inhibitory effects for TEA and L-carnitine uptake. The presence of an outward H(+) gradient induced a marked stimulation of TEA uptake, whereas it induced no stimulation of L-carnitine uptake. Furthermore, unlabeled TEA preloaded in the vesicles markedly enhanced [14C]TEA uptake, but unlabeled L-carnitine did not stimulate [14C]TEA uptake. These results suggest that transport of TEA across brush-border membranes is independent of the Na(+)/L-carnitine cotransport activity, and organic cation secretion across brush-border membranes is predominantly mediated by the H(+)/organic cation antiporter. 相似文献
124.
Sato T Ozaki R Kamo S Hara Y Konishi S Isobe Y Saitoh S Harada H 《Biochimica et biophysica acta》2003,1622(3):145-150
2',3'-Dihydrophylloquinone (dihydro-K1) is a hydrogenated form of vitamin K1 (K1), which is produced during the hydrogenation of K1-rich plant oils. In this study, we found that dihydro-K1 counteracts the sodium warfarin-induced prolonged blood coagulation in rats. This indicates that dihydro-K1 functions as a cofactor in the posttranslational gamma-carboxylation of the vitamin K-dependent coagulation factors. It was also found that dihydro-K1 as well as K1 inhibits the decreasing effects of warfarin on the serum total osteocalcin level. In rats, dihydro-K1 is well absorbed and detected in the tissues of the brain, pancreas, kidney, testis, abdominal aorta, liver and femur. K1 is converted to menaquinone-4 (MK-4) in all the above-mentioned tissues, but dihydro-K1 is not. The unique characteristic of dihydro-K1 possessing vitamin K activity and not being converted to MK-4 would be useful in revealing the as yet undetermined physiological function of the conversion of K1 to MK-4. 相似文献
125.
Shimizu A Asakawa S Sasaki T Yamazaki S Yamagata H Kudoh J Minoshima S Kondo I Shimizu N 《Biochemical and biophysical research communications》2003,309(1):143-154
We identified a novel giant gene encoding a transmembrane protein with CUB and sushi multiple domains on the human chromosome 8q23.3-q24.1 in which benign adult familial myoclonic epilepsy type 1 (BAFME1/FAME, OMIM:601068) has been mapped. This giant gene consists of 73 exons and spans over 1.2Mb on the genomic DNA region. It showed significant homology to two genes, CSMD1 gene on 8p23 and CSMD2 gene on 1p34, at reduced amino acid sequence level and hence we designated as CSMD3. The CSMD3 gene was expressed mainly in adult and fetal brains. We performed mutation analysis on the CSMD3 gene for seven patients with BAFME1/FAME, but no mutation was found in the coding sequence of the CSMD3 gene. Comparative genomic analysis revealed a conserved family of CSMD genes in the mouse and fugu genomes. Possible functions of the CSMD gene family are discussed. 相似文献
126.
An environmentally benign and stereoselective beta-mannopyranosylation has been developed employing 4,6-O-benzylidene-protected mannopyranosyl diethyl phosphite as a glycosyl donor and montmorillonite K-10 as an activator. 相似文献
127.
The cDNA encoding a second type of mouse beta-galactoside alpha2,6-sialyltransferase (ST6Gal II) was cloned and characterized. The sequence of mouse ST6Gal II encoded a protein of 524 amino acids and showed 77.1% amino acid sequence identity with human ST6Gal II. Recombinant ST6Gal II exhibited alpha2,6-sialyltransferase activity toward oligosaccharides that have the Galbeta1,4GlcNAc sequence at the nonreducing end of their carbohydrate groups, but it exhibited relatively low and no activity toward some glycoproteins and glycolipids, respectively. On the other hand, ST6Gal I, which has been known as the sole member of the ST6Gal-family for more than ten years, exhibited broad substrate specificity toward oligosaccharides, glycoproteins, and a glycolipid, paragloboside. The ST6Gal II gene was mainly expressed in brain and embryo, whereas the ST6Gal I gene was ubiquitously expressed, and its expression levels were higher than those of the ST6Gal II gene. The ST6Gal II gene is located on chromosome 17 and spans over 70 kb of mouse genomic DNA consisting of at least 6 exons. The ST6Gal II gene has a similar genomic structure to the ST6Gal I gene. In this paper, we have shown that ST6Gal II is a counterpart of ST6Gal I. 相似文献
128.
Ozaki T Ambe S Minai Y Enomoto S Yatagai F Abe T Yoshida S Makide Y 《Biological trace element research》2001,84(1-3):197-211
Interaction of elements in the course of element uptake by carrot (Daucas carota cv. U.S. harumakigosun) exerted by the addition of elements, such as Rb, Zn, and Al, was investigated. For the purpose of precise evaluation of uptake behavior, the simultaneous determination of absorption of Na, Be, Sr, Mn, Co, Zn, Ce, Pm, and Gd was conducted by the multitracer technique. For root uptakes, Al exhibited its influence on the uptake of essential elements and on the uptake of toxic or unbeneficial ones, presumably as a result of the large electric valency that caused cell membrane disintegrity. On the other hand, Zn as a divalent cation only affected the uptake of essential and beneficial elements. Rubidium, which is a monovalent cation, did not exhibit any effect on the uptake of other ions. Concerning shoot uptakes, inhibition by Zn and Al, but not by Rb, was observed for the uptake of Sr, Mn, Co, and Zn. From the present investigation, it is suggested that there exists an interaction between added ions and the elements taken into plants and that the degree of interaction increases in the increasing order of ionic valency: M+ (Rb), M2+ (Zn), and M3+ (Al). 相似文献
129.
Weiming Zheng Junichi Izaki Shuichi Furusawa Yukinori Yoshimura 《Biological procedures online》2001,3(1):1-7
We established a sensitive non-radioactive in situ hybridization (ISH) method for the detection of chicken IgG γ-chain mRNA in paraffin sections. RNA probes were transcribed
in vitro fromcloned chicken IgG CH1 nucleotide sequences with SP6/T7 RNA polymerases in the presence of DIG-UTP. These probes
were used for hybridization and were immunodetected using anti-DIG antibodies conjugated to horseradish peroxidase. The immunoreactive
products were visualized with DAB-H2O2. IgG γ-chain mRNA-expressing cells were localized in both the spleen and oviductal tissues. This method demonstrated an excellent
sensitivity since the ISH signal was clear and the background was negligible. We found that in the spleen IgG γ-chain mRNA-expressing
cells were present mainly in the red pulp, whereas in the oviduct they appeared mainly in the mucosal stroma and not in the
mucosal epithelium.
Published: May 14, 2001. 相似文献
130.