全文获取类型
收费全文 | 653篇 |
免费 | 63篇 |
出版年
2021年 | 8篇 |
2020年 | 8篇 |
2019年 | 12篇 |
2018年 | 8篇 |
2017年 | 6篇 |
2016年 | 19篇 |
2015年 | 22篇 |
2014年 | 20篇 |
2013年 | 31篇 |
2012年 | 24篇 |
2011年 | 32篇 |
2010年 | 19篇 |
2009年 | 19篇 |
2008年 | 30篇 |
2007年 | 33篇 |
2006年 | 37篇 |
2005年 | 28篇 |
2004年 | 24篇 |
2003年 | 23篇 |
2002年 | 27篇 |
2001年 | 25篇 |
2000年 | 26篇 |
1999年 | 21篇 |
1998年 | 14篇 |
1997年 | 10篇 |
1996年 | 9篇 |
1995年 | 5篇 |
1994年 | 10篇 |
1993年 | 6篇 |
1992年 | 14篇 |
1991年 | 11篇 |
1990年 | 14篇 |
1989年 | 14篇 |
1988年 | 13篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 13篇 |
1984年 | 8篇 |
1983年 | 9篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1976年 | 5篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有716条查询结果,搜索用时 843 毫秒
1.
Troponin T (TNT) expressed in the developing chicken cardiac muscle was examined by immunoblotting combined with two-dimensional electrophoresis (2-D PAGE) and peptide mapping. When the whole lysate of the neonatal heart was examined by 2-D PAGE, two TNT variants were detected on the gel by monoclonal antibody to TNT. Expression of the two variants was developmentally regulated: one isoform (type I) was expressed from embryonic through neonatal stages, and the other (type II) from the late embryonic stage through adulthood during cardiac muscle development. The type-I isoform, but not type-II isoform, was also expressed transiently in chicken skeletal muscle at embryonic stages. As judged from the peptide maps, the two isoforms differed in the N-terminal region but not in the C-terminal region. 相似文献
2.
S-100 Protein in Clonal Astroglioma Cells Is Released by Adrenocorticotropic Hormone and Corticotropin-Like Intermediate-Lobe Peptide 总被引:4,自引:1,他引:3
Fujiko Suzuki Kanefusa Kato Taiji Kato Nobuaki Ogasawara 《Journal of neurochemistry》1987,49(5):1557-1563
S-100 protein in clonal GA-1 and C6 rat glioma cell lines was released in serum-free medium supplemented with adrenocorticotropic hormone (ACTH). The induction of S-100 protein release by ACTH was dose-dependent, showing a half-maximal release at about 5 microM, and the S-100 protein concentration in the medium increased sharply within 3 min, but slightly during further incubation. The S-100 protein release was apparently accompanied by a decrease in the membrane-bound form of S-100 protein in the cell. The S-100 protein release was induced not by the ACTH1-24 fragment, which exhibits the known effects of ACTH, but by the ACTH18-39 fragment, which is designated as corticotropin-like intermediate-lobe peptide (CLIP). These results indicate that the C-terminal half of ACTH is responsible for the S-100 protein release. The enhancement of S-100 protein release by ACTH was also observed in normal rat glioblasts. The release induced by ACTH was apparently specific to S-100 protein, because little release of the cytoplasmic enzymes, creatine kinase, and enolase was observed under the same conditions. High concentrations (5 mM) of dibutyryl cyclic AMP or dibutyryl cyclic GMP were also found to induce S-100 protein release; however, catecholamines (epinephrine, norepinephrine, isoproterenol, and dopamine), acetylcholine, and glutamic acid did not enhance the release.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
4.
Shin Fujimori Naoyuki Kamatani Yutaro Nishida Nobuaki Ogasawara Ieo Akaoka 《Human genetics》1990,84(5):483-486
Summary A previously undescribed nucleotide substitution at codon 51 (CGA to TGA) has been identified using the polymerase chain reaction technique in hypoxanthine guanine phosphoribosyltransferase (HPRT) cDNA; this is the first molecular evidence for a point mutation in a Japanese patient with Lesch-Nyhan syndrome. The present mutation is the 19th nucleotide substitution identified as a germ-line mutation at this locus and the second mutation generating a stop codon. The position of the nucelotide substitution is exactly the same as a previously described mutation HPRTToronto, indicating for the first time that nucleotide substitutions at the same position in the sequence of HPRT can generate different mutant alleles, one causing a partial deficiency and the other a complete deficiency. Although the type of nucleotide substitution is different between the two cases, a single base position has twice become the target of a mutation. However, the calculation of the probability of finding substitution mutations at the same base position in the coding region of hprt indicates that there is no evidence for the presence of a hot spot for substitution mutations in the human hprt germ line. 相似文献
5.
Human IFN-gamma production is inhibited by a synthetic peptide homologous to retroviral envelope protein 总被引:6,自引:0,他引:6
M Ogasawara G J Cianciolo R Snyderman M Mitani R A Good N K Day 《Journal of immunology (Baltimore, Md. : 1950)》1988,141(2):614-619
A synthetic 17 amino acid peptide (CKS-17) homologous to a highly conserved region of human and animal retroviral transmembrane proteins was investigated for its influence on the in vitro production of IFN-gamma from human peripheral mononuclear cells. The results showed that CKS-17 coupled to a carrier protein, BSA, inhibited production of IFN-gamma in a dose-dependent manner. Controls, consisting of BSA, which had undergone the coupling procedure or neurotensin coupled to BSA in an identical manner as CKS-17, showed no such inhibition. Reduction in IFN-gamma production could not be attributed to decreased viability of cells, delay of IFN-gamma production or to involvement of suppressor cells. Moreover, inhibition of IFN-gamma production was not related to the inhibition of DNA synthesis. The inhibition appeared to be a direct effect of CKS-17 on IFN-gamma-producing cells. Kinetic studies revealed that this suppression occurred when CKS-17 was introduced to the culture concurrent with or within 48 h after introduction of IFN inducers. Preincubation experiments showed that the presence of CKS-17 in the culture medium was not necessary to exert its inhibitory effect. These results suggest that a portion of retroviral envelope proteins possess important immunomodulatory actions. 相似文献
6.
The in vitro activity of several new imidazoles, cloconazole, sulconazole, butoconazole, isoconazole and fenticonazole, were compared with those of amphothericin B, flucytosine, and three azoles: econazole, miconazole and ketoconazole against isolates of pathogenic Candida. A total of 186 clinical isolates of 10 species of the genus Candida and two culture collection strains were tested by an agar-dilution technique. Isoconazole was the most active azole, followed by butoconazole and sulconazole. Differences between some of the species in their susceptibility to the antifungal agents were noted. Sulconazole and cloconazole had the highest activity in vitro against 106 isolates of C. albicans. Butoconazole and isoconazole were also very active against isolates of C. albicans, and were the most active azole compounds against 80 isolates of Candida spp. 相似文献
7.
Yasukazu Yamada Haruko Goto Kaoru Suzumori Ritsuko Adachi Nobuaki Ogasawara 《Human genetics》1992,90(4):379-384
Five independent mutations in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene were identified in a partially HPRT deficient patient with gout and in four Lesch-Nyhan patients. Using the polymerase chain reaction (PCR) technique coupled with direct sequencing, the nucleotide sequences of the entire HPRT coding region amplified from the cDNA and also of each exon amplified form the genomic DNA were analyzed. Three independent point mutations in the coding region were detected in the partially HPRT deficient patient (Case 1) and in two Lesch-Nyhan patients (Case 2 and 3), resulting in single amino acid substitutions. The family study of Case 3, utilizing a PvuII restriction site created in the mutant gene, indicated that the mother was a heterozygote, and a sister and a fetal brother had inherited the normal HPRT gene from the mother. In two other mutants causing Lesch-Nyhan syndrome, a portion of the HPRT gene was deleted, and RNA splicing was missing in both mutants. A 4-bp deletion at the 5 end of exon 4 resulted in formation of three different types of abnormal mRNA (Case 4). The other mutant (Case 5) produced abnormal mRNA including 26bp of intron 8 instead of the deleted 58bp at the 5 end of exon 9, because of a 74-bp deletion from intron 8 to exon 9. 相似文献
8.
When confluent cultures of cloned mouse 3T3-L1 cells were differentiated to adipocytes by three days of treatment with a combination of 0.5 microM dexamethasone and 0.5 mM 1-methyl-3-isobutylxanthine, the S100 protein content in the cells increased markedly, as determined by a sensitive immunoassay system. The S100 protein induced in the cell was the alpha alpha form (S100ao), which is the predominant form of S100 protein in mouse adipose tissue. The S100ao concentration in preadipocytes was about 1-3 ng/mg protein, while the concentration in differentiated adipocytes was 60-200 ng/mg protein. The immunoblotting test of the crude extract of adipocytes confirmed that the immunoreactive substance in the cells was the alpha subunit of S100 protein. The treatment with 1-methyl-3-isobutylxanthine or dexamethasone alone neither elicited the S100 protein induction nor triacylglycerols accumulation in the cells. The accumulation of triacyglycerols in the cells was always preceded by the induction of S100ao protein under conditions where the differentiation to adipocytes was elicited. The induction of S100ao protein and accumulation of triacylglycerols in the cells treated with dexamethasone and 1-methyl-3-isobutylxanthine were inhibited by the addition of antimicrotubular drugs, colchicine and vinblastine, but not by cytochalasin B, an antimicrofilament drug. S100ao protein in 3T3-L1 adipocytes was released by incubation with a lipolytic hormone, adrenocorticotropic hormone or catecholamines, in a cyclic-AMP-dependent manner as observed with rat epididymal fat pads [Biochim. Biophys. Acta (1986) 889, 84-90]. These results also suggest that S100 protein may participate in the function of adipocytes. 相似文献
9.
Interaction of the Bacillus subtilis DnaA-like protein with the Escherichia coli DnaA protein. 总被引:5,自引:2,他引:3 下载免费PDF全文
Plasmids carrying the intact Bacillus subtilis dnaA-like gene and two reciprocal hybrids between the B. subtilis and Escherichia coli dnaA genes were constructed. None of the plasmids could transform wild-type E. coli cells unless the cells contained surplus E. coli DnaA protein (DnaAEc). A dnaA (Ts) strain integratively suppressed by the plasmid R1 origin could be transformed by plasmids carrying either the B. subtilis gene (dnaABs) or a hybrid gene containing the amino terminus of the E. coli gene and the carboxyl terminus of the B. subtilis gene (dnaAEc/Bs). In cells with surplus E. coli DnaA protein, expression of the E. coli dnaA gene was derepressed by the B. subtilis DnaA protein and by the hybrid DnaAEc/Bs protein, whereas it was strongly repressed by the reciprocal hybrid protein DnaABs/Ec. The plasmids carrying the different dnaA genes probably all interfere with initiation of chromosome replication in E. coli by decreasing the E. coli DnaA protein concentration to a limiting level. The DnaABs and the DnaAEc/Bs proteins effect this decrease possibly by forming inactive oligomeric proteins, while the DnaABs/Ec protein may decrease dnaAEc gene expression. 相似文献
10.
Bovine mitochondrial DNA polymorphism in restriction endonuclease cleavage patterns and the location of the polymorphic sites 总被引:2,自引:0,他引:2
Tomomasa Watanabe Yukimasa Hayashi Reiji Semba Nobuaki Ogasawara 《Biochemical genetics》1985,23(11-12):947-957
Cleavage patterns of mitochondrial DNA (mtDNA) by restriction endonuclease analysis were examined in four Japanese Black cows, three Japanese Shorthorn cows, and six Holstein cows. Seventeen restriction enzymes which recognize six base pairs and two restriction enzymes which recognize four base pairs were used in this study. Polymorphism was observed with three restriction enzymes, HindIII, TaqI, and MspI, and was detected within the breeds. Nucleotide substitution was determined in the HindIII polymorphic site by DNA cloning and sequencing; this is C----T at position 10126 of the URF-3 region. Furthermore, the MspI and TaqI polymorphic sites were located on the physical map. 相似文献