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排序方式: 共有357条查询结果,搜索用时 15 毫秒
1.
M E Sant A Poiner M C Harsanyi S D Lyons R I Christopherson 《Analytical biochemistry》1989,182(1):121-128
A number of antagonists of nucleotide metabolism with anti-cancer activity affect the de novo purine pathway. To determine the biochemical mechanisms of cytotoxicity of these drugs, assay procedures have been developed for measurement of the levels of intermediates proximal to IMP in the pathway for de novo purine biosynthesis in mouse L1210 leukemia cells. Purine precursors have been synthesized in vitro from [14C]glycine using enzymes from chicken liver. These 14C-labeled intermediates have been used as marker compounds to define retention times for metabolites of leukemia cells separated by HPLC and the chromatographic mobilities of these intermediates after two-dimensional thin-layer chromatography. These new chromatographic procedures have been used in combination to determine the steady-state concentrations for purine precursors in mouse L1210 leukemia cells in the exponential phase of growth: N-formylglycineamide ribotide (16 microM); N-formylglycineamidine ribotide (4.7 microM); 5-aminoimidazole ribotide (4.0 microM); 4-carboxy-5-aminoimidazole ribotide (0.46 microM); N-succino-5-aminoimidazole-4-carboxamide ribotide (11 microM); 5-aminoimidazole-4-carboxamide ribotide (16 microM); 5-formamidoimidazole-4-carboxamide ribotide (2.7 microM); and IMP (57 microM). The metabolic effects of tiazofurin (25 microM) upon mouse L1210 leukemia cells growing in culture define a "metabolic crossover point" at the reaction catalyzed by IMP dehydrogenase (EC 1.1.1.205) which confirms previous reports of inhibition of this enzyme. 相似文献
2.
R I Christopherson K J Schmalzl E Szabados R J Goodridge M C Harsanyi M E Sant E M Algar J E Anderson A Armstrong S C Sharma 《Biochemistry》1989,28(2):463-470
In mammals, dihydroorotase is part of a trifunctional protein, dihydroorotate synthetase, which catalyzes the first three reactions of de novo pyrimidine biosynthesis. Dihydroorotase catalyzes the formation of a peptide-like bond between the terminal ureido nitrogen and the beta-carboxyl group of N-carbamyl-L-aspartate to yield heterocyclic L-dihydroorotate. A variety of evidence suggests that dihydroorotase may have a catalytic mechanism similar to that of a zinc protease [Christopherson, R. I., & Jones, M. E. (1980) J. Biol. Chem. 255, 3358-3370]. Tight-binding inhibitors of the zinc proteases, carboxypeptidase A, thermolysin, and angiotensin-converting enzyme have been synthesized that combine structural features of the substrates with a thiol or carboxyl group in an appropriate position to coordinate a zinc atom bound at the catalytic site. We have synthesized (4R)-2-oxo-6-thioxohexahydropyrimidine-4-carboxylate (L-6-thiodihydroorotate) and have found that this analogue is a potent competitive inhibitor of dihydroorotase with a dissociation constant (Ki) in the presence of excess Zn2+ ion of 0.17 +/- 0.02 microM at pH 7.4. The potency of inhibition by L-6-thiodihydroorotate in the presence of divalent metal ions decreases in the order Zn2+ greater than Ca2+ greater than Co2+ greater than Mn2+ greater than Ni2+; L-6-thiodihydroorotate alone is less inhibitory and has a Ki of 0.85 +/- 0.14 microM. 6-Thioorotate has a Ki of 82 +/- 8 microM which decreases to 3.8 +/- 1.4 microM in the presence of Zn2+. Zn2+ alone is a moderate inhibitor of dihydroorotase and does not enhance the potency of other inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
The growth of mustard was increased significantly when treated with up to 80 kg N ha–1 (N80). Spraying with (2-chloroethyl) trimethylammoniumchloride (chlormequat chloride) increased seed yield and seed protein content. Spraying nitrogen fertilized plots with chlormequat chloride, increased leaf area, leaf area ratio, leaf area duration, number of siliquae plant–1, number of seeds siliqua–1 and length of siliqua. Reducing, non-reducing and total sugars in the leaves at 80 days after sowing were also affected significantly. Chlorophyll a, b and total chlorophyll were little affected. The number of siliquae plant–1 was highly correlated with seed yield in both the seasons of experimentation. The correlation coefficient value () was 0.586 in 1982/83 and 0.912 in 1983/84.The total accumulation of nutrients, i.e. nitrogen, phosphorus and potassium in seed and straw was significantly affected by N80 × chlormequat chloride interaction. 相似文献
4.
Prem Kumar Dantu Sant S. Bhojwan 《Journal of plant biochemistry and biotechnology.》1992,1(2):115-118
Effect of some physical and chemical factors on in vitro shoot multiplication in Gladioius was investigated. A modified MS medium with NH4NO3 reduced to half strength, KH2PO4 replaced with 300 mg/l of NaH2PO4 2 H2O and Kl omitted completely, was found to be better than the original MS. BAP was better than either kinetin or 2iP. Of the various physical factors studied, the propagule size, light and container volume influenced the rate of shoot multiplication. On the modified medium containing 0.5 mg/l BAP in dark, the propagules bearing 20 buds showed 8-fold multiplication. 相似文献
5.
6.
Peter Van t Sant Albert M. Kroon 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,739(1):57-65
In a previous paper (Van 't Sant, P., Mak, J.F.C. and Kroon, A.M. (1981) Eur. J. Biochem. 121, 21–26) we showed the existence of three elongated precursor proteins (45, 36 and 25 kDa) of mitochondrial translation products in Neurospora crassa. We presented some indications that the largest precursor could be related to subunit 1 of cytochrome c oxidase. Here we present conclusive evidence that the 45-kDa polypeptide is indeed this precursor by demonstrating that an immunodetectable 45-kDa polypeptide displays the same behaviour as the labeled 45-kDa precursor; both accumulate after long incubation with cycloheximide or by decreasing the temperature and both are not tightly membrane bound. Moreover the antibody against subunit 1 of cytochrome c oxidase also recognizes, in immunoadsorption experiments, besides subunit 1, the 45-kDa polypeptide accumulated by cycloheximide incubation. Furthermore, we developed a small scale purification of antibodies against subunit 1 of cytochrome c oxidase. By means of these purified antibodies it is demonstrated that the 45-kDa polypeptide and subunit 1 have corresponding antigenic determinants. Under the various conditions tested, all three precursors are less firmly membrane-bound than the mature subunits. Finally, it is observed that in short incubations in vivo, chloramphenicol inhibits the processing of the mitochondrially synthesized precursors, under conditions where mitochondrial translation is only partially inhibited. 相似文献
7.
Direct sequencing of the mitochondrial displacement loop (D-loop) of shrews
(genus Sorex) for the region between the tRNA(Pro) and the conserved
sequence block-F revealed variable numbers of 79-bp tandem repeats. These
repeats were found in all 19 individuals sequenced, representing three
subspecies and one closely related species of the masked shrew group (Sorex
cinereus cinereus, S. c. miscix, S. c. acadicus, and S. haydeni) and an
outgroup, the pygmy shrew (S. hoyi). Each specimen also possessed an
adjacent 76-bp imperfect copy of the tandem repeats. One individual was
heteroplasmic for length variants consisting of five and seven copies of
the 79-bp tandem repeat. The sequence of the repeats is conducive to the
formation of secondary structure. A termination-associated sequence is
present in each of the repeats and in a unique sequence region 5' to the
tandem array as well. Mean genetic distance between the masked shrew taxa
and the pygmy shrew was calculated separately for the unique sequence
region, one of the tandem repeats, the imperfect repeat, and these three
regions combined. The unique sequence region evolved more rapidly than the
tandem repeats or the imperfect repeat. The small genetic distance between
pairs of tandem repeats within an individual is consistent with a model of
concerted evolution. Repeats are apparently duplicated and lost at a high
rate, which tends to homogenize the tandem array. The rate of D- loop
sequence divergence between the masked and pygmy shrews is estimated to be
15%-20%/Myr, the highest rate observed in D-loops of mammals. Rapid
sequence evolution in shrews may be due either to their high metabolic rate
and short generation time or to the presence of variable numbers of tandem
repeats.
相似文献
8.
9.
大鼠胼胝体内神经肽Y免疫反应阳性纤维的发育 总被引:1,自引:0,他引:1
本实验用免疫组织化学ABC法研究了大鼠胼胝体内神经肽Y免疫反应阳性(NPY-IR)纤维的生后发育。结果发现,许多NPY-IR纤维在大鼠出生时便存在于胼胝体内。NPY-IR胼胝体纤维的密度在生后1周内继续逐渐增高,在第2周内达到最高峰。之后,NPY-IR胼胝体纤维的密度逐渐下降,至第3周末时接近成年时的水平,即仅有少量NPY-IR纤维存在于胼胝体内。这些结果提示在大鼠早期生后发育过程中许多NPY-IR胼胝体纤维是暂时性的,其作用可能与大脑皮质的机能发育有关。 相似文献
10.
Herpes simplex virus 1 alpha regulatory protein ICP0 interacts with and stabilizes the cell cycle regulator cyclin D3. 总被引:16,自引:12,他引:4 下载免费PDF全文
The herpes simplex virus 1 (HSV-1) infected-cell protein 0 (ICP0) has the characteristics of a promiscuous transactivator of genes introduced into cells by infection or transfection. To identify cellular proteins interacting with ICP0, we used a domain of exon II of ICP0 that is known to be crucial for regulatory function of the protein as bait in the yeast two-hybrid screen. Our results were as follows. (i) A cDNA in a positive yeast colony was found to encode cyclin D3, a cell cycle regulator of G1 phase. (ii) A purified chimeric protein consisting of glutathione S-transferase (GST) fused to cyclin D3 specifically formed complexes with ICP0 contained in HSV-1-infected cell lysate. (iii) To enhance the expression of cyclin D3, the gene was inserted into the viral genome and overexpressed in infected cells. The overexpressed cyclin D3 colocalized with ICP0 in nuclear structures characteristic of ND10 and which earlier have been reported to contain ICP0. (iv) The accumulation of cyclin D3 protein in Vero cells infected with an alpha0 deletion mutant was reduced relative to that of cells infected with wild-type virus or a recombinant virus in which the deleted alpha0 sequences were restored. (v) Lysates of Spodoptera frugiperda Sf9 cells doubly infected with baculoviruses genetically engineered to express cyclin D3 and cyclin-dependent kinase 4 (CDK4) phosphorylated GST fused to retinoblastoma protein (GST-pRb) but did not phosphorylate the GST-alpha0(20-241) or GST-alpha0(543-768) fusion protein or immunoprecipitated ICP0 proteins. Moreover, the chimeric GST-ICP0(exon II) protein shown to bind cyclin D3 had no effect on the activity of the kinase on GST-pRb when added to mixtures of lysates of Sf9 cells which coexpressed cyclin D3 and CDK4. These results indicate that ICP0 interacts with, colocalizes with, and stabilizes the cyclin D3 cell cycle regulator and does not affect its interaction with the cyclin-dependent kinase. 相似文献