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1.
Dual Cyclin-Binding Domains Are Required for p107 To Function as a Kinase Inhibitor 总被引:11,自引:6,他引:5 下载免费PDF全文
Enrique Castao Yelena Kleyner Brian David Dynlacht 《Molecular and cellular biology》1998,18(9):5380-5391
The retinoblastoma (pRB) family of proteins includes three proteins known to suppress growth of mammalian cells. Previously we had found that growth suppression by two of these proteins, p107 and p130, could result from the inhibition of associated cyclin-dependent kinases (cdks). One important unresolved issue, however, is the mechanism through which inhibition occurs. Here we present in vivo and in vitro evidence to suggest that p107 is a bona fide inhibitor of both cyclin A-cdk2 and cyclin E-cdk2 that exhibits an inhibitory constant (Ki) comparable to that of the cdk inhibitor p21/WAF1. In contrast, pRB is unable to inhibit cdks. Further reminiscent of p21, a second cyclin-binding site was mapped to the amino-terminal portions of p107 and p130. This amino-terminal domain is capable of inhibiting cyclin-cdk2 complexes, although it is not a potent substrate for these kinases. In contrast, a carboxy-terminal fragment of p107 that contains the previously identified cyclin-binding domain serves as an excellent kinase substrate although it is unable to inhibit either kinase. Clustered point mutations suggest that the amino-terminal domain is functionally important for cyclin binding and growth suppression. Moreover, peptides spanning the cyclin-binding region are capable of interfering with p107 binding to cyclin-cdk2 complexes and kinase inhibition. Our ability to distinguish between p107 and p130 as inhibitors rather than simple substrates suggests that these proteins may represent true inhibitors of cdks. 相似文献
2.
D. V. Popov D. V. Swirkun A. I. Netreba O. S. Tarasova A. B. Prostova I. M. Larina A. S. Borovik O. L. Vinogradova 《Human physiology》2006,32(5):609-614
The study was designed to test the hypothesis that, during strength training, a restricted blood supply to the working muscles stimulates the secretion of anabolic hormones and an increase in the muscle mass and strength can be achieved with significantly lower training loads. During eight weeks, three times a week, 18 young, physically active males trained their leg extensor muscles. Nine subjects (group I) worked at 80% of the maximal voluntary contraction (MVC), whereas the rest (group II) performed their exercise without relaxation and at a lower load (50% MVC). The total training load in group II was significantly lower than in group I (77 ± 5 vs. 157 ± 7 kJ, respectively). The eight-week training of both groups significantly increased the mean maximum strength (by 35 and 21% in groups I and II, respectively) and volume (by 17 and 9%, respectively) of the muscles trained (however, the differences between the groups with respect to these changes were nonsignificant). Group I displayed a higher increase in the blood level of creatine phosphokinase than group II, while group II showed a greater increase in the blood concentration of lactate. In contrast to group I, group II displayed a significant increase in the blood concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), and cortisol. Hence, the suggestion that the secretion of metabolic hormones is triggered by a metabolic, rather than mechanical, stimulus from working muscles seems plausible. 相似文献
3.
O A Kovalenko N I Tarasova A G Ivannikova L N Voronkova T G Nikolaeva 《Tsitologiia》1989,31(4):447-452
The effect of picolinic acid (PA) on SPEV cell proliferation is found to be different from that on normal and virus transformed NRC cells, and on spontaneously transformed CHO cells. It is shown that SPEV cells are arrested by PA at the end of G1-phase and at the beginning of S-phase and probably in G2-phase of the cell cycle. Ferrous ions remove the G1/S block induced by PA to permit the cell transfer through S-phase. On the one hand, PA chelates ferrous ions from the cells, and on the other one it inhibits the replicative DNA synthesis. It can be suggested that PA may arrest the SPEV cell growth affecting the iron-depend stable radical formation which is introduced into the active centre of ribonucleotiDE reduCTase. This results in the lower enzyme activity. 相似文献
4.
V I Kiselev I M Tarasova A Iu Malinin O I Kiselev A I Glukhov 《Molekuliarnaia genetika, mikrobiologiia i virusologiia》1988,(9):21-26
A thermoresistant htpR mutant having a decreased level of proteolytic activity has been selected in E. coli strain K802 after the directed mutagenesis in vivo. The mutation results in the bacteriophage T7 RNA-polymerase stability, aminoglycosidephosphotransferase stability as well as in the decrease in the rate of proteolytic degradation of cytoplasmic proteins during the heat shock. The obtained mutant strain can, probably be used as a host for alien polypeptides production. 相似文献
5.
B A Zamotin L S Naumovich G S Tarasova M V Anisimova 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1986,(4):40-44
The general tendency of a decrease in the morbidity rates of dysentery induced by Shigella sonnei and Shigella flexneri (separately) from Monday to the end of the week (Saturday-Sunday) has been revealed, and at the same time the "infection risk" for both kinds of salmonellosis has been found to fall on the last days of the week (Friday-Sunday). 相似文献
6.
The data on changes in the partial pressure of carbon dioxide (pCO2) dissolved in the fermentation broth in the course of biosynthesis of tetracycline made in a 63 m3 fermenter are presented. It is shown that pCO2 equal approximately to 2 cPa was optimal for tetracycline biosynthesis. The total carbonate concentration and pCO2 were estimated simultaneously in the process of tetracycline fermentation. 相似文献
7.
8.
M. Fujinaga M. M. Chernaia N. I. Tarasova S. C. Mosimann M. N. James 《Protein science : a publication of the Protein Society》1995,4(5):960-972
The three-dimensional crystal structure of human pepsin and that of its complex with pepstatin have been solved by X-ray crystallographic methods. The native pepsin structure has been refined with data collected to 2.2 A resolution to an R-factor of 19.7%. The pepsin:pepstatin structure has been refined with data to 2.0 A resolution to an R-factor of 18.5%. The hydrogen bonding interactions and the conformation adopted by pepstatin are very similar to those found in complexes of pepstatin with other aspartic proteinases. The enzyme undergoes a conformational change upon inhibitor binding to enclose the inhibitor more tightly. The analysis of the binding sites indicates that they form an extended tube without distinct binding pockets. By comparing the residues on the binding surface with those of the other human aspartic proteinases, it has been possible to rationalize some of the experimental data concerning the different specificities. At the S1 site, valine at position 120 in renin instead of isoleucine, as in the other enzymes, allows for binding of larger hydrophobic residues. The possibility of multiple conformations for the P2 residue makes the analysis of the S2 site difficult. However, it is possible to see that the specific interactions that renin makes with histidine at P2 would not be possible in the case of the other enzymes. At the S3 site, the smaller volume that is accessible in pepsin compared to the other enzymes is consistent with its preference for smaller residues at the P3 position. 相似文献
9.
10.
L M Iakunitskaia M A Samartsev G V Tarasova V F Martynov 《Prikladnaia biokhimiia i mikrobiologiia》1980,16(2):232-237
The conditions for subtilishine BPN' binding with bromocyanogen activated dextranes have been selected. The dependence of the enzyme activity and stability from pH and temperature levels has been studied. The stability of a modified enzyme during storage in solution is increased as compared with that of the native enzyme due to a decrease in the autolysis rate. On the basis of diffusion coefficients and sedimentation constants of conjugates, absolute values of their molecular weights have been computed. 相似文献