全文获取类型
收费全文 | 1473篇 |
免费 | 227篇 |
专业分类
1700篇 |
出版年
2021年 | 31篇 |
2020年 | 11篇 |
2019年 | 12篇 |
2018年 | 16篇 |
2017年 | 12篇 |
2016年 | 25篇 |
2015年 | 37篇 |
2014年 | 38篇 |
2013年 | 78篇 |
2012年 | 56篇 |
2011年 | 59篇 |
2010年 | 43篇 |
2009年 | 35篇 |
2008年 | 50篇 |
2007年 | 56篇 |
2006年 | 49篇 |
2005年 | 52篇 |
2004年 | 62篇 |
2003年 | 52篇 |
2002年 | 44篇 |
2001年 | 48篇 |
2000年 | 56篇 |
1999年 | 42篇 |
1998年 | 19篇 |
1997年 | 18篇 |
1996年 | 20篇 |
1995年 | 12篇 |
1994年 | 17篇 |
1993年 | 18篇 |
1992年 | 35篇 |
1991年 | 47篇 |
1990年 | 47篇 |
1989年 | 28篇 |
1988年 | 37篇 |
1987年 | 28篇 |
1986年 | 30篇 |
1985年 | 28篇 |
1984年 | 18篇 |
1983年 | 14篇 |
1982年 | 21篇 |
1981年 | 14篇 |
1979年 | 14篇 |
1978年 | 16篇 |
1977年 | 11篇 |
1976年 | 17篇 |
1975年 | 16篇 |
1974年 | 17篇 |
1973年 | 19篇 |
1970年 | 23篇 |
1968年 | 18篇 |
排序方式: 共有1700条查询结果,搜索用时 0 毫秒
11.
Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. 总被引:103,自引:0,他引:103
A new human cyclin, named cyclin E, was isolated by complementation of a triple cln deletion in S. cerevisiae. Cyclin E showed genetic interactions with the CDC28 gene, suggesting that it functioned at START by interacting with the CDC28 protein. Two human genes were identified that could interact with cyclin E to perform START in yeast containing a cdc28 mutation. One was CDC2-HS, and the second was the human homolog of Xenopus CDK2. Cyclin E produced in E. coli bound and activated the CDC2 protein in extracts from human G1 cells, and antibodies against cyclin E immunoprecipitated a histone H1 kinase from HeLa cells. The interactions between cyclin E and CDC2, or CDK2, may be important at the G1 to S transition in human cells. 相似文献
12.
The objective of this study was to determine if radiotelemetry could be used to measure myometrial electromyographic (EMG) activity. A radio transmitter with one pair of biopotential leads was implanted in the flank ipsilateral to the pregnant uterine horn at least five weeks prior to the expected date of parturition in two mares. The biopotential leads were implanted in the base of the pregnant uterine horn. Telemetered data were received by a pair of antennae placed at right angles in a 3.3 by 6.6-m stall. Data were recorded on VHS format videocassette tapes continuously for the 24h prior to and following parturition. Simultaneous physiograph recordings were made as a hard copy reference. In addition, 10 mg of prostaglandin F(2alpha) was administered to two mares in the luteal phase of the estrous cycle. Myometrial EMG during parturition was increased similarly to that of previously published reports that used myometrial electrodes wired directly to a physiograph. Prostaglandin F(2alpha) also caused an increase in myometrial EMG activity within 8 min of administration. This study demonstrated that radiotelemetry can be used for measuring myometrial EMG activity. 相似文献
13.
14.
A glycosylphosphatidylinositol protein anchor from procyclic stage Trypanosoma brucei: lipid structure and biosynthesis. 下载免费PDF全文
Cells of the insect (procyclic) stage of the life cycle of the African trypanosome, Trypanosoma brucei, express an abundant stage-specific glycosylated phosphatidylinositol (GPI) anchored glycoprotein, the procyclic acidic repetitive protein (PARP). The anchor is insensitive to the action of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC), suggesting that it contains an acyl-inositol. We have recently described the structure of a PI-PLC resistant glycosylphosphatidylinositol, PP1, which is specific to the procyclic stage, and have presented preliminary evidence that the phosphatidylinositol portion of the protein-linked GPI on PARP has a similar structure. In this paper we show, by metabolic labelling with [3H]fatty acids, that the PARP anchor contains palmitate esterified to inositol, and stearate at sn-1, in a monoacylglycerol moiety, a structure identical to PP1. Using pulse-chase labelling, we show that both fatty acids are incorporated into the GPI anchor from a large pool of metabolic precursors, rather than directly from acyl-CoA. We also demonstrate that the addition of the GPI anchor moiety to PARP is dependent on de novo protein synthesis, excluding the possibility that incorporation of fatty acids into PARP can occur by a remodelling of pre-existing GPI anchors. Finally we show that the phosphatidylinositol (PI) species that are utilized for GPI biosynthesis are a subpopulation of the cellular PI molecular species. We propose that these observations may be of general validity since several other eukaryotic membrane proteins (e.g. human erythrocyte acetylcholine esterase and decay accelerating factor) have been reported to contain palmitoylated inositol residues. 相似文献
15.
Maternal cigarette smoking, Down syndrome in live births, and infant race. 总被引:1,自引:1,他引:0 下载免费PDF全文
Previous studies have suggested that maternal smoking is negatively associated with a Down syndrome live birth. We analyzed the data of the U.S. Perinatal Collaborative Study in a search for racial variation in Down syndrome risk factors. There were 22 cases in 25,346 live births to smoking mothers (4/10,780 blacks, 18/13,320 whites, and 0/1,246 other races) and 42/29,130 live births to nonsmoking mothers (24/14,665 blacks, 14/11,694 whites, and 4/2,771 others). The crude overall rates per 1,000 live births were 0.4 in black smokers and 1.6 in black nonsmokers but 1.4 in white smokers and 1.2 in white non-smokers. Adjusted for maternal age, the summary relative risk for a Down syndrome live birth to a smoking mother was 0.2 in blacks (95% interval 0.1-0.7) but 1.2 in whites (95% interval 0.6-2.5). Stratification on variables associated with socioeconomic status or gestational age at time of entry into the study did not alter the racial difference. A comparison of smokers with those who never smoked revealed essentially the same trends. Among all nonsmokers the ratio of the maternal age-adjusted risks for a Down syndrome live birth in whites compared with blacks was 0.7 (95% interval 0.3-1.3), and among all smokers this ratio was 3.6 (95% interval 1.3-9.9). If the results are not attributable to statistical fluctuation or undetected confounding, then differences in the probability of intrauterine survival of the Down syndrome fetus would appear to be one plausible explanation for the difference. 相似文献
16.
The ATP binding site on rho protein. Affinity labeling of Lys181 by pyridoxal 5'-diphospho-5'-adenosine 总被引:7,自引:0,他引:7
A J Dombroski J R LaDine R L Cross T Platt 《The Journal of biological chemistry》1988,263(35):18810-18815
We have labeled the nucleoside triphosphate-binding domain of Escherichia coli rho factor with the ATP affinity analog [3H]pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP). PLP-AMP completely inactivates the RNA-dependent ATPase activity of rho upon incorporation of 3 mol of reagent/mol of hexameric rho protein. Although the potency of PLP-AMP is enhanced when an RNA substrate such as poly(C) is present, the stoichiometry for inhibition remains the same as in the absence of poly(C). The nucleotide substrate ATP competes very effectively for the binding site and protects against PLP-AMP inactivation. A domain of rho called N2, which comprises the distal two-thirds of the molecule (residues 152-419) and encompasses the region proposed to bind ATP, is labeled specifically in the presence of poly(C). Amino acid sequence analysis of the single [3H]PLP-AMP labeled proteolytic fragment showed Lys181 to be the site of modification, suggesting that this residue normally interacts with the gamma-phosphoryl of bound ATP. These results agree with our proposed tertiary structure for the ATP-binding domain of rho that places this lysine residue in a flexible loop above a hydrophobic nucleotide-binding pocket comprised of several parallel beta-strands, similar to adenylate kinase, F1-ATPase, and related ATP-binding proteins. Parallel studies of rho structure and function by site-directed mutagenesis and chemical modification support this interpretation. 相似文献
17.
The adenine nucleotide analog, [3H]pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP), is shown to be a potent and specific inhibitor of yeast hexokinase PII. Evidence that the analog binds specifically at the ATP binding site includes the demonstration that glucose binding enhances PLP-AMP binding and that PLP-AMP and ATP bind competitively with an apparent Ki(PLP-AMP) = 23 microM. In addition, from the relationship between the degree of inhibition and extent of modification, it is estimated that the incorporation of 1 mol of PLP-AMP/mol of subunit is required for complete inhibition. Borohydride reduction of the Schiff's base complex formed between hexokinase and [3H]PLP-AMP gives a stable product. The reduced derivative was digested with trypsin and a single radioactive peptide was isolated by reversed-phase high-pressure liquid chromatography. Amino acid sequence analysis identified Lys-111 as the modified residue. Taking into account the known structures of the binary complexes (Shoham, M., and Steitz, T. A. (1980) J. Mol. Biol. 140, 1-14), the results suggest that Lys-111, located in the smaller of the two lobes of hexokinase, moves into the active site upon formation of the ternary complex. 相似文献
18.
Ewa Nizankowska Angelita Q. Sheridan Marie H. Maile Carol J. Cross Rafal Nizankowski Krystyna Prochowska Andrew Szczeklik 《Prostaglandins & other lipid mediators》1985,29(3):349-362
We evaluated in a double-blind study the bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1 (PGE1-carbinol), described recently as a nonirritant bronchodilator in animals. Fifteen asthmatic patients received by inhalation single doses of 1, 10, and 30 μg PGE1-carbinol, 55 μg PGE2, and placebo (10% ethanol in normal saline, which was also used as diluent for the PGs). Such pulmonary function tests as forced expiratory volume in 1 second, forced vital capacity, and maximal expiratory flow were monitored during 2 hours following inhalation of each compound. 10 and 30 μg PGE1-carbinol produced significant but short-acting bronchodilation, similar to that caused by 55 μg PGE2. One-third of the patients reported mild cough and throat irritation during and shortly after inhalation of 30 μg PGE1-carbinol or 55 μg PGE2. Placebo and 1 μg PGE1-carbinol produced minimal side effects, but neither agent caused bronchodilation. In an adjunctive, unblinded trial, the same patients received 400 μg fenoterol. Fenoterol caused greater bronchodilation 15 and 30 minutes after inhalation than did the PGs in the double-blind study. 相似文献
19.
20.
We have constructed mutants of Rous sarcoma virus expressing p60src that are underphosphorylated on serine or tyrosine, by linker insertion or insertion/ deletion into cloned Rous sarcoma virus DNA, and recovery of mutant virus by transfection of chicken embryo fibroblasts. Cells infected with mutants whose p60src lack the major site of either serine or tyrosine phosphorylation were morphologically transformed and formed colonies in soft agar. The tyrosine kinase activities of the mutant p60src measured in vivo and in vitro were close to the wild type activity. Peptide mapping showed that phosphorylation on tyrosine and serine of p60src is independent: the major phosphorylated tyrosine and the major phosphorylated serine can each be phosphorylated in the absence of phosphorylation of the other. 相似文献