全文获取类型
收费全文 | 605篇 |
免费 | 71篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 2篇 |
2019年 | 11篇 |
2018年 | 11篇 |
2017年 | 8篇 |
2016年 | 11篇 |
2015年 | 26篇 |
2014年 | 32篇 |
2013年 | 39篇 |
2012年 | 37篇 |
2011年 | 28篇 |
2010年 | 18篇 |
2009年 | 26篇 |
2008年 | 36篇 |
2007年 | 37篇 |
2006年 | 27篇 |
2005年 | 32篇 |
2004年 | 30篇 |
2003年 | 16篇 |
2002年 | 25篇 |
2001年 | 20篇 |
2000年 | 18篇 |
1999年 | 11篇 |
1998年 | 17篇 |
1997年 | 8篇 |
1996年 | 6篇 |
1995年 | 8篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 11篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 6篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1974年 | 2篇 |
1973年 | 6篇 |
1967年 | 3篇 |
排序方式: 共有676条查询结果,搜索用时 31 毫秒
1.
John S. Adams Mercedes A. Gacad Andrew J. Baker Benjamin Gonzales Robert K. Rude 《American journal of primatology》1985,9(3):219-224
We measured the serum concentration of 25-hydroxyvitamin D3 (25-OH-D3) and 1,25-dihydroxyvitamin D3 (1,25-[OH]2-D3) in 23 different Platyrrhines from four different genera and in 21 Catarrhines from six different genera in residence at the Los Angeles Zoo. The mean (±S.E.) serum concentration of 1,25-(OH)2-D3 was significantly greater in Platyrrhines (810 ± 119 pg/ml) than in Catarrhines (61 ± 5 pg/ml), suggesting that high circulating concentrations of the active vitamin D hormone were a characteristic of New World primates in both the Cebidae and Callitrichidae family. This increase in the serum concentration of 1,25-(OH)2-D3 is probably an adaptational response on the part of Platyrrhini to offset a relative decrease in the concentration of specific receptor for 1,25-(OH)2-D3 in target tissues for the hormone. 相似文献
2.
Amy Chapman Gonzalo Gonzales Wayne R. Burrowes Paul Assanah Bernadette Iannone Michael K. Leung George B. Stefano 《Cellular and molecular neurobiology》1984,4(2):143-155
In Mytilus and Leucophaea the high-affinity binding site density is significantly lower in old animals than in young animals, whereas the low-affinity site density remains unchanged. In Mytilus the estimated met-enkephalin and met-enkephalin-Arg6-Phe7 levels are significantly higher in old than in young animals. In Leucophaea only the met-enkephalin level can be determined, and it is also higher in old animals. The decrease in the high-affinity binding site density and the corresponding increase in endogenous enkephalin levels suggest the existence of an opioid compensatory mechanism associated with the aging process. In Mytilus there is a demonstrated decrease with age in intraganglionic dopamine levels in response to applied opiates. In addition, the inhibition of dopamine-stimulated adenylate cyclase activity by opiates also decreases in older animals. In Leucophaea the sex difference in opioid binding densities diminishes with age. 相似文献
3.
4.
Purification of plasmid DNA by fast protein liquid chromatography on superose 6 preparative grade 总被引:1,自引:0,他引:1
We were able to reduce both the time and the use of hazardous chemicals associated with the previous plasmid isolation methods of high-pressure liquid chromatography and CsCl gradient centrifugation by employing fast protein liquid chromatography (FPLC). Plasmid was first crudely prepared from bacterial cultures by a standard alkaline lysis method. After an alcohol precipitation, the nucleic acids were divided into two equal portions. One half was used for a standard purification method employing CsCl centrifugation. The other was dissolved in FPLC buffer, treated with RNase A, and applied to a Superose 6 preparative grade column (HR 10/30). Plasmid eluted off the column within 20 min as a single, highly resolved peak. Plasmid isolated by FPLC had yields, purity, and transformation efficiencies similar to that isolated by CsCl centrifugation. 相似文献
5.
M L Gonzales A Basu G H de Haas R Dijkman M G van Oort A A Okolo R H Glew 《Archives of biochemistry and biophysics》1988,262(1):345-353
The study of the acidic lipid requirement of human spleen glucocerebrosidase was extended to include two new series of acidic lipids, namely, monoacylglycol sulfates and diacylglycerol sulfates. Lysosomal glucocerebrosidase was extracted with sodium cholate and 1-butanol to render its beta-glucosidase activity dependent upon exogenous lipids. Maximum reactivation of control glucocerebrosidase was obtained with nonanoylglycol sulfate (NGS) and diheptanoylglycerol sulfate (DHGS). However, the effects of these lipids were markedly dependent on the nature of buffer used in the assay medium; specifically, 0.2 M sodium citrate-phosphate (pH 5.5) was much more effective than 0.2 M sodium acetate (pH 5.5) in permitting these lipids to reactivate glucocerebrosidase. In contrast, the marked activation of glucocerebrosidase by phosphatidylserine and galactocerebroside 3-sulfate (sulfatide) that was achievable in the sodium acetate buffer was totally inhibited by citrate or phosphate ions. The effects of NGS and DHGS on the kinetic parameters of control glucocerebrosidase were to lower the Km for the substrate, 4-methylumbelliferyl-beta-D-glucoside from 5.5 mM to approximately 2 mM (in sodium citrate-phosphate buffer) and markedly increase the Vmax. Furthermore, with DHGS, significant activation was achieved at concentrations below the lipid's critical micellar concentration. None of the monoacylglycol- or diacylglycerol sulfates were capable of stimulating mutant glucocerebrosidases from either type 1 (Ashkenazi-Jewish) or type 2 Gaucher's disease patients. Like control glucocerebrosidase, the type 1 glucocerebrosidase was unresponsive to phosphatidylserine and sulfatide when the beta-glucosidase assay was conducted in 0.2 M sodium citrate-phosphate buffer. Based on the differential action of these lipid activators in the two buffers and their effects on the mutant enzymes, we propose that, with regard to the lipid requirement of glucocerebrosidase, there are two classes of acidic lipids--one comprised of phosphatidylserine and sulfatide and the other comprised of the likes of NGS, DHGS, or sodium taurodeoxycholate. It appears that control glucocerebrosidase and the mutant enzyme of the patient with type 1 Gaucher's disease is reconstitutable with the first class of lipids whereas the glucocerebrosidase of the type 2 patient is not. The observations in this report are interpreted in terms of a model which postulates that normal glucocerebrosidase possesses at least two distinct lipid binding domains. 相似文献
6.
7.
Linda W. Gonzales Stanley Meizel 《Biochimica et Biophysica Acta (BBA)/General Subjects》1973,320(1):180-194
Five acid phosphatases, S4, S3, S2, Szn and S1 (orthophosphoric monoester phosphohydrolase, EC 3.1.3.2) of ejaculated rabbit spermatozoa were either partially purified by DEAE-Sephadex column chromatography or prepared by specific extraction methods.The pH optimum of S4 was 6.0–6.5 in acetate buffer and 7.0 in Tris-HCl buffer; the pH optima of S3, S2, Szn, and S1 were 4.5, 5.5., 6.0 and 5.2, respectively, in acetate buffer. The apparent molecular weights of S3, S, Szn and S1, determined by disc gel electrophoresis, were 123 000, 86 000, 64 000 and 45 000–49 000, respectively. Incubation with neuraminidase did not alter the electrophoretic mobilities of any of the enzymes.Ten natural phosphoric esters were tested as substrates. S4 preferentially hydrolyzed ATP, ADP, PPi and 3′-AMP. S3 hydrolyzed only β-glycerophosphate and glucose 6-phosphate to a significant extent. S2 hydrolyzed β-glycerophosphate, glucose 1-phosphate, the phosphoproteins, casein and phosvitin. S1 hydrolyzed ADP and β-glycerophosphate most readily. Szn may be an ATPase since it exhibits very high Zn2+-stimulated against ATP.These characteristics combined with the effects of NaF, ZnCl2, l-(+)-tartaric acid, and formaldehyde on the activity of each partially purified enzyme with α-naphthyl phosphate as substrate indicate that these phosphatases are structurally and functionally different. 相似文献
8.
9.
B M Fraij P J Birckbichler M K Patterson K N Lee R A Gonzales 《The Journal of biological chemistry》1992,267(31):22616-22623
A 1.9-kilobase (kb) cDNA for a new transglutaminase protein has been cloned and sequenced from retinoic acid-induced human erythroleukemia (HEL) cells. Full-length cDNA analysis reveals an open reading frame coding for a polypeptide of 548 amino acid residues with a molecular weight of 61,740. The deduced amino acid sequence exhibited 98% identity to the human cellular transglutaminase sequence. The cysteine at position 277 in the active site and the putative Ca(2+)-binding pocket at residues 446-453 of cellular transglutaminase are conserved. Such evidence predicts that the encoded protein product is likely to be a transglutaminase homologue (TGase-H). Immunoprecipitation of the in vitro translation products from a synthetic TGase-H mRNA and from total protein of cultured erythroleukemia HEL cells revealed a protein with a molecular weight of 63,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Northern blot analysis of HEL cells and normal human fibroblast cells WI-38 using a cellular TGase probe detected the 1.9- and 4.0-kb RNA species at a relative abundance of 1:3 and 1:7, respectively. The 3'-end of the human cellular transglutaminase mRNA was also cloned and sequenced to allow comparison to the 3'-end of TGase-H reported here. This new piece gives a full length of 4012 nucleotides (4.0 kb) for human cellular transglutaminase. Comparison of the 5'-end (bases 1-1747) of the 1.9- and 4.0-kb cDNA sequences revealed a very high degree of identity. Beginning with base 1748, the sequences diverge showing no homology. The divergence point correlates with known intron-exon consensus boundaries indicative of alternative splicing. 相似文献
10.
C. W. Bird B. C. Baculis J. J. Mayfield G. J. Chavez T. Ontiveros D. J. Paine A. J. Marks A. L. Gonzales D. Ron C. F. Valenzuela 《Genes, Brain & Behavior》2019,18(3)
Prenatal exposure to alcohol causes a wide range of deficits known as fetal alcohol spectrum disorders (FASDs). Many factors determine vulnerability to developmental alcohol exposure including timing and pattern of exposure, nutrition and genetics. Here, we characterized how a prevalent single nucleotide polymorphism in the human brain‐derived neurotrophic factor (BDNF) gene (val66met) modulates FASDs severity. This polymorphism disrupts BDNF's intracellular trafficking and activity‐dependent secretion, and has been linked to increased incidence of neuropsychiatric disorders such as depression and anxiety. We hypothesized that developmental ethanol (EtOH) exposure more severely affects mice carrying this polymorphism. We used transgenic mice homozygous for either valine (BDNFval/val) or methionine (BDNFmet/met) in residue 68, equivalent to residue 66 in humans. To model EtOH exposure during the second and third trimesters of human pregnancy, we exposed mice to EtOH in vapor chambers during gestational days 12 to 19 and postnatal days 2 to 9. We found that EtOH exposure reduces cell layer volume in the dentate gyrus and the CA1 hippocampal regions of BDNFmet/met but not BDNFval/val mice during the juvenile period (postnatal day 15). During adulthood, EtOH exposure reduced anxiety‐like behavior and disrupted trace fear conditioning in BDNFmet/met mice, with most effects observed in males. EtOH exposure reduced adult neurogenesis only in the ventral hippocampus of BDNFval/val male mice. These studies show that the BDNF val66met polymorphism modulates, in a complex manner, the effects of developmental EtOH exposure, and identify a novel genetic risk factor that may regulate FASDs severity in humans. 相似文献