全文获取类型
收费全文 | 50087篇 |
免费 | 3661篇 |
国内免费 | 19篇 |
出版年
2023年 | 181篇 |
2022年 | 584篇 |
2021年 | 949篇 |
2020年 | 591篇 |
2019年 | 703篇 |
2018年 | 1047篇 |
2017年 | 945篇 |
2016年 | 1528篇 |
2015年 | 2397篇 |
2014年 | 2747篇 |
2013年 | 3095篇 |
2012年 | 4060篇 |
2011年 | 3893篇 |
2010年 | 2471篇 |
2009年 | 2252篇 |
2008年 | 3124篇 |
2007年 | 3013篇 |
2006年 | 2643篇 |
2005年 | 2445篇 |
2004年 | 2250篇 |
2003年 | 1939篇 |
2002年 | 1680篇 |
2001年 | 1372篇 |
2000年 | 1319篇 |
1999年 | 1055篇 |
1998年 | 428篇 |
1997年 | 384篇 |
1996年 | 285篇 |
1995年 | 244篇 |
1994年 | 234篇 |
1993年 | 211篇 |
1992年 | 389篇 |
1991年 | 336篇 |
1990年 | 316篇 |
1989年 | 281篇 |
1988年 | 221篇 |
1987年 | 212篇 |
1986年 | 171篇 |
1985年 | 145篇 |
1984年 | 119篇 |
1983年 | 118篇 |
1982年 | 108篇 |
1981年 | 86篇 |
1980年 | 85篇 |
1979年 | 128篇 |
1978年 | 100篇 |
1977年 | 92篇 |
1976年 | 70篇 |
1975年 | 75篇 |
1974年 | 92篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
191.
Junhyong Kim Mark A. Burgman 《Evolution; international journal of organic evolution》1988,42(3):596-602
A comparative study of the accuracy of three different approaches to phylogenetic estimation was made on simulated data with differing rates of change in different lineages. The three approaches were maximum likelihood, maximum parsimony, and phenetic clustering. The data were generated by simulating genetic drift with different population sizes over a simple four-species tree topology. Although the accuracy of all three approaches was found to be dependent on the number of loci (characters), maximum likelihood was found to perform considerably and consistently better than maximum parsimony or phenetic clustering. 相似文献
192.
Characterization of New Punch Mutations: Identification of Two Additional Mutant Classes 总被引:2,自引:2,他引:0 下载免费PDF全文
The Punch locus of Drosophila melanogaster which encodes the pteridine biosynthetic enzyme, GTP cyclohydrolase, is genetically complex. Lethal alleles of the locus resolve into an array of interallelic complementation groups, and at least one class of mutations is developmentally specific, affecting GTP cyclohydrolase activity only in the heads of adults. All previously isolated Punch alleles were identified on the basis of a mutant eye color phenotype. By screening mutagenized chromosomes over Punch region deficiencies, we have now isolated new alleles on the basis of lethal and visible phenotypes. Most of these alleles fall into previously identified genetic classes, but two new classes of mutations were also found. One class contains two alleles that behave as dominant lethal mutations in some genetic backgrounds. The other class represents a second developmentally specific set of alleles that affect the function of the Punch locus only during embryogenesis. 相似文献
193.
K E Schwartz B Zaro J Reynolds J Duffy T Saito J S Hunt H Sevelius 《Hormones et métabolisme》1988,20(10):637-640
Enprostil, a long-acting, orally active dehydroprostaglandin E2 with cytoprotective and gastric antisecretory properties, is a potent inhibitor of meal-stimulated gastrin release. Recent data have suggested suppression of additional other gastrointestinal peptide hormones following single doses of enprostil. The current investigation was conducted to further clarify the effects of enprostil administration on gastrointestinal hormones and glucose metabolism under physiologic conditions and to determine whether these effects were present following multiple doses of the agent. Enprostil 70 mcg/d and its placebo were each administered for 7 1/2 days to eight normal male subjects in a study of crossover design, each treatment period lasting 7 1/2 days and separated by a 7 day washout period. Subjects received a test meal on days 1 and 8 and an oral glucose challenge on day 3 of each treatment period following enprostil or its placebo. Following the test meal, there was a delay and suppression of the maximum measured serum glucose levels. Mean overall peak glucose concentrations were lower during the enprostil phase compared to placebo (112 vs. 121 mg/dd, P = 0.025) with a trend toward delay in the time to achievement of peak glucose concentrations. Mean overall peak levels for insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) were significantly suppressed by 36%, 16% and 60%, respectively by enprostil when compared to placebo. The overall integrated postprandial responses for insulin, C-peptide, and GIP were significantly reduced by 42%, 39% and 90%, respectively while that for glucose above baseline was reduced by 44% (P = 0.098). Similar effects were present following the oral glucose challenge.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
194.
195.
Site in the cat-86 regulatory leader that permits amicetin to induce expression of the gene. 总被引:6,自引:3,他引:3 下载免费PDF全文
U J Kim N P Ambulos Jr E J Duvall M A Lorton P S Lovett 《Journal of bacteriology》1988,170(7):2933-2938
Expression of the plasmid gene cat-86 is induced in Bacillus subtilis by two antibiotics, chloramphenicol and the nucleoside antibiotic amicetin. We proposed that induction by either drug causes the destabilization of a stem-loop structure in cat-86 mRNA that sequesters the ribosome-binding site for the cat coding sequence. The destabilization event frees the ribosome-binding site, permitting the initiation of translation of cat-86 mRNA. cat-86 induction is due to the stalling of a ribosome in a leader region of cat-86 mRNA, which is located 5' to the RNA stem-loop structure. A stalled ribosome that is active in cat-86 induction has its aminoacyl site occupied by leader codon 6. To test the hypothesis that a leader site 5' to codon 6 permits a ribosome to stall in the presence of an inducing antibiotic, we inserted an extra codon between leader codons 5 and 6. This insertion blocked induction, which was then restored by the deletion of leader codon 6. Thus, induction seems to require the maintenance of a precise spatial relationship between an upstream leader site(s) and leader codon 6. Mutations in the ribosome-binding site for the cat-86 leader, RBS-2, which decreased its strength of binding to 16S rRNA, prevented induction. In contrast, mutations that significantly altered the sequence of RBS-2 but increased its strength of binding to 16S rRNA did not block induction by either chloramphenicol or amicetin. We therefore suspected that the proposed leader site that permitted drug-mediated stalling was located between RBS-2 and leader codon 6. This region of the cat-86 leader contains an eight-nucleotide sequence (conserved region I) that is largely conserved among all known cat leaders. The codon immediately 5' to conserved region I differs, however, between amicetin-inducible and amicetin-noninducible cat genes. In amicetin-inducible cat genes such as cat-86, the codon 5' to conserved region I is a valine codon, GTG. The same codon in amicetin-noninducible cat genes is a lysine codon, either AAA or AAG. When the GTG codon immediately 5' to conserved region I in cat-86 was changed to AAA, amicetin was no longer active in cat-86 induction, but chloramphenicol induction was unaffected by the mutation. The potential role of the GTG codon in amicetin induction is discussed. 相似文献
196.
Affinity purification of human deoxycytidine kinase: avoidance of structural and kinetic artifacts arising from limited proteolysis 总被引:2,自引:0,他引:2
Homogeneous deoxycytidine kinase has been isolated from leukemic human T-lymphoblasts by affinity chromatography based on a multisubstrate analog, deoxycytidine 5'-adenosine 5"'-P1,P4-tetraphosphate (dCp4A). Chromatography of extract treated with protease inhibitors yielded a monomeric polypeptide, inasmuch as the Mr of the native protein, 59,300, is comparable to the value of 52,000 from sodium dodecyl sulfate polyacrylamide gel electrophoresis. The isoelectric pH was 6.1. But, enzyme isolated without protease inhibitors exhibited two fragments of Mr = 30,000 and 33,000, suggesting that proteolytic cleavage of the parental polypeptide had occurred during affinity chromatography. Both the parental and proteolyzed enzymes phosphorylated deoxyadenosine and deoxyguanosine, as well as deoxycytidine. However, the proteolyzed enzyme had an increased apparent Km for deoxycytidine. In consequence of this, a mixture of the two forms produced bimodal kinetic plots, whereas linear kinetics were displayed by each form alone. 相似文献
197.
Membrane-associated NAD+ glycohydrolase from rabbit erythrocytes is solubilized by phosphatidylinositol-specific phospholipase C 总被引:1,自引:0,他引:1
NAD+ glycohydrolase (NADase) present on the surface of rabbit erythrocytes is a membrane-bound ectoenzyme that can be solubilized by phosphatidylinositol-specific phospholipase C (PIPLC). As much as 70% of the cell-associated NADase was made soluble by treatment with PIPLC. The portion of NADase that remained cell-associated after an initial PIPLC treatment proved to be resistant to subsequent solubilization attempts. Further analysis showed that release of NADase from erythrocytes could not be attributed to the action of proteinases or phospholipase C. Erythrocytes obtained from other mammals were analyzed and found to have variable amounts of PIPLC-susceptible NADase. Practically, this finding can be used to easily solubilize membrane-bound NADase as a first step in its purification. 相似文献
198.
Acetate kinase purified from Acinetobacter calcoaceticus was inhibited by diethylpyrocarbonate with a second-order rate constant of 620 M-1.min-1 at pH 7.4 at 30 degrees C and showed a concomitant increase in absorbance at 240 nm due to the formation of N-carbethoxyhistidyl derivative. Activity could be restored by hydroxylamine and the pH curve of inactivation indicates the involvement of a residue with a pKa of 6.64. Complete inactivation of acetate kinase required the modification of seven residues per molecule of enzyme. Statistical analysis showed that among the seven modifiable residues, only one is essential for activity. 5,5'-dithiobis(2-nitrobenzoic acid), p-chloromercuryphenylsulfonate, N-ethylmaleimide and phenylglyoxal did not affect the enzyme activity. These results suggest that the inactivation is due to the modification of one histidine residue. The substrates, acetate and ATP, protected the enzyme against inactivation, indicating that the modified histidine residue is located at or near the active site. 相似文献
199.
J F Templeton V P Kumar D Bose D D Smyth R S Kim F S LaBella 《Canadian journal of physiology and pharmacology》1988,66(11):1420-1424
The synthesis of the glucoside, 3 beta-[(beta-D-glucopyranosyl)oxy]-14-hydroxy-14 beta-pregn-4-en-20-one, a 14 beta-hydroxyprogesterone glucoside (14 beta-OHP-glu), is described. This compound has an IC50 of 1 microM in a [3H]ouabain binding assay, and is about 10 times more potent than the aglycone. Like 14 beta-hydroxyprogesterone, the glucoside enhances contractility of isolated cardiac muscle. 14 beta-OHP-glu or ouabain, when infused at comparable doses into the renal artery of the anesthetized rat, markedly increases urine volume. Whereas ouabain significantly enhances urinary potassium excretion with little or no effect on sodium excretion, 14 beta-OHP-glu promotes a marked natriuresis with no significant effect on potassium excretion. 相似文献
200.
R J Linhardt K G Rice Y S Kim J D Engelken J M Weiler 《The Journal of biological chemistry》1988,263(26):13090-13096
This paper demonstrates that heparin-oligosaccharides with low anticoagulant activity have a high capacity to inhibit activation of the amplification pathway of complement in vitro. We prepared heparin-oligosaccharides by partial depolymerization of heparin using purified flavobacterial heparinase. The resulting oligosaccharide mixture was then fractionated using strong anion exchange-high pressure liquid chromatography to produce individual oligosaccharide components of this mixture, with degree of polymerization ranging from 2 to 16. These heparin-oligosaccharides were examined for both their anticoagulant activity and capacity to inhibit activation of the amplification pathway of complement. Although there was little difference among commercial heparins, a correlation between molecular weight and activity to inhibit convertase generation was clearly established for heparin-oligosaccharides between degree of polymerization 2 through 16. Heparin-oligosaccharides of degree of polymerization 10-16 (Mr 3888-5320) demonstrated up to 54% of heparin's activity on a molar basis (and up to 163% of heparin's activity on a weight basis) in inhibiting the amplification pathway of complement in vitro while showing almost no anticoagulant activity. These studies, for the first time, completely separate heparin's ability to inhibit complement activation from its anticoagulant activity. 相似文献