全文获取类型
收费全文 | 57923篇 |
免费 | 4602篇 |
国内免费 | 4511篇 |
专业分类
67036篇 |
出版年
2024年 | 142篇 |
2023年 | 789篇 |
2022年 | 1855篇 |
2021年 | 3049篇 |
2020年 | 2084篇 |
2019年 | 2506篇 |
2018年 | 2345篇 |
2017年 | 1806篇 |
2016年 | 2547篇 |
2015年 | 3635篇 |
2014年 | 4391篇 |
2013年 | 4442篇 |
2012年 | 5294篇 |
2011年 | 4765篇 |
2010年 | 2887篇 |
2009年 | 2599篇 |
2008年 | 2939篇 |
2007年 | 2635篇 |
2006年 | 2263篇 |
2005年 | 1888篇 |
2004年 | 1513篇 |
2003年 | 1424篇 |
2002年 | 1072篇 |
2001年 | 909篇 |
2000年 | 889篇 |
1999年 | 810篇 |
1998年 | 503篇 |
1997年 | 454篇 |
1996年 | 477篇 |
1995年 | 425篇 |
1994年 | 414篇 |
1993年 | 327篇 |
1992年 | 446篇 |
1991年 | 324篇 |
1990年 | 284篇 |
1989年 | 260篇 |
1988年 | 210篇 |
1987年 | 194篇 |
1986年 | 176篇 |
1985年 | 154篇 |
1984年 | 115篇 |
1983年 | 122篇 |
1982年 | 81篇 |
1981年 | 46篇 |
1980年 | 51篇 |
1979年 | 63篇 |
1976年 | 46篇 |
1974年 | 54篇 |
1973年 | 45篇 |
1972年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 9 毫秒
871.
Ziheng Yang 《Journal of molecular evolution》1995,40(6):689-697
Several maximum likelihood and distance matrix methods for estimating phylogenetic trees from homologous DNA sequences were compared when substitution rates at sites were assumed to follow a gamma distribution. Computer simulations were performed to estimate the probabilities that various tree estimation methods recover the true tree topology. The case of four species was considered, and a few combinations of parameters were examined. Attention was applied to discriminating among different sources of error in tree reconstruction, i.e., the inconsistency of the tree estimation method, the sampling error in the estimated tree due to limited sequence length, and the sampling error in the estimated probability due to the number of simulations being limited. Compared to the least squares method based on pairwise distance estimates, the joint likelihood analysis is found to be more robust when rate variation over sites is present but ignored and an assumption is thus violated. With limited data, the likelihood method has a much higher probability of recovering the true tree and is therefore more efficient than the least squares method. The concept of statistical consistency of a tree estimation method and its implications were explored, and it is suggested that, while the efficiency (or sampling error) of a tree estimation method is a very important property, statistical consistency of the method over a wide range of, if not all, parameter values is prerequisite. 相似文献
872.
873.
874.
催产素在脊髓水平对电针镇痛的影响 总被引:3,自引:0,他引:3
采用玻璃微电极胞外记录和脊髓表面给药的方法观察了催产素(OT)、抗催产素血清(AOTS)以及电针穴位对背角神经元伤害性诱发放电的影响。结果表明:电针穴位或脊髓表面施加OT可部分抑制脊髓背角神经元的伤害性诱发放电;在电针的基础上施加OT则明显加强电针的抑制效应;相反,用AOTS预处理后,电针的抑制作用放取消。提示OT在脊髓水平参与了对痛觉信息的调制,并与一定频率的针刺镇痛有关。 相似文献
875.
The N-terminal -amino groups of 1-bungarotoxin (1-Bgt) fromBungarus multicinctus venom were modified with trinitrobenzene sulfonic acid and the modified derivative was separated by high performance liquid chromatography. The trinitrophenylated (TNP) derivative contained two TNP groups at the -amino groups of A chain and B chain and showed a marked decrease in enzymatic activity. Methionine residues at positions 6 and 8 of the A chain were oxidized with chloramine T or cleaved with cyanogen bromide to remove the N-terminal octapeptide. Oxidation of methionine residues and removal of the N-terminal octapeptide caused a precipitous decrease in enzymatic activity, whereas antigenicity remained unchanged. The presence of dihexanoyllecithin influenced the interaction between 1-Bgt and 8-antilinonaphthalene sulfonate (ANS) and revealed that 1-Bgt consists of two types of ANS-binding sites, one at the substrate binding site of the A chain and the other might be at the B chain. The modified derivatives still retained their affinity for Ca2+ and ANS, indicating that the N-terminal region is not involved in Ca2+ and substrate binding. A fluorescence study revealed that the -amino group of the A chain was in the vicinity of substrate binding site and that the TNP -amino groups were in proximity to Trp-19 of the A chain. In addition, the study showed that the N-terminal region is important for stabilizing the architectural environment of Trp-19. The results, together with the proposal that Trp-19 of the A chain is involved in substrate binding, suggest that the N-terminal region of the A chain plays a crucial role in maintaining a functional active site for 1-Bgt. 相似文献
876.
Dephosphorylation of the beta 2-adrenergic receptor and rhodopsin by latent phosphatase 2 总被引:1,自引:0,他引:1
S D Yang Y L Fong J L Benovic D R Sibley M G Caron R J Lefkowitz 《The Journal of biological chemistry》1988,263(18):8856-8858
Recent evidence suggests that the function of receptors coupled to guanine nucleotide regulatory proteins may be controlled by highly specific protein kinases, e.g. rhodopsin kinase and the beta-adrenergic receptor kinase. In order to investigate the nature of the phosphatases which might be involved in controlling the state of receptor phosphorylation we studied the ability of four highly purified well characterized protein phosphatases to dephosphorylate preparations of rhodopsin or beta 2-adrenergic receptor which had been highly phosphorylated by beta-adrenergic receptor kinase. These included: type 1 phosphatase, calcineurin phosphatase, type 2A phosphatase, and the high molecular weight latent phosphatase 2. Under conditions in which all the phosphatases could dephosphorylate such common substrates as [32P]phosphorylase a and [32P]myelin basic protein at similar rates only the latent phosphatase 2 was active on the phosphorylated receptors. Moreover, a latent phosphatase activity was found predominantly in a sequestered membrane fraction of frog erythrocytes. This parallels the distribution of a beta-adrenergic receptor phosphatase activity recently described in these cells (Sibley, D. R., Strasser, R. H., Benovic, J. L., Daniel, K., and Lefkowitz, R. J. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 9408-9412). These data suggest a potential role for the latent phosphatase 2 as a specific receptor phosphatase. 相似文献
877.
878.
Molecular cloning of the cDNA for the catalytic subunit of human DNA polymerase delta. 总被引:3,自引:0,他引:3 下载免费PDF全文
C L Yang L S Chang P Zhang H Hao L Zhu N L Toomey M Y Lee 《Nucleic acids research》1992,20(4):735-745
The cDNA of human DNA polymerase delta was cloned. The cDNA had a length of 3.5 kb and encoded a protein of 1107 amino acid residues with a calculated molecular mass of 124 kDa. Northern blot analysis showed that the cDNA hybridized to a mRNA of 3.4 kb. Monoclonal and polyclonal antibodies to the C-terminal 20 residues specifically immunoblotted the human pol delta catalytic polypeptide. A multiple sequence alignment was constructed. This showed that human pol delta is closely related to yeast pol delta and the herpes virus DNA polymerases. The levels of pol delta message were found to be induced concomitantly with DNA pol delta activity and DNA synthesis in serum restimulated proliferating IMR90 cultured cells. The human pol delta gene was localized to chromosome 19 by Southern blotting of EcoRI digested DNA from a panel of rodent/human cell hybrids. 相似文献
879.
Studies are described examining further the decline in folate analogue influx mediated by the one-carbon reduced-folate transport system in HL-60 cells following induction of maturation by cytodifferentiation agents. To facilitate the investigation of the underlying basis of this phenomenon, we derived a variant (HL-60/LCV) with 4-5-fold elevated influx capacity (Vmax) for folate analogues. A commensurate increase in the putative transporter for this system was documented by affinity labeling of these cells with N-hydroxysuccinimide-[3H]aminopterin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity labeled plasma membrane in HL-60/LCV cells delineated a protein peak at Mr = 75,000-80,000. This was substantially greater than the analogous transporter (Mr = 45,000-47,000) we had delineated (Yang, C.-H., Sirotnak, F.M., and Mines, L.S. (1988) J. Biol. Chem. 263, 9703-9709) with the same methodology in the L1210 cell plasma membrane. In addition, the rate of translocation of the Mr = 75,000-80,000 transporter in HL-60 and HL-60/LCV cells was 2-fold lower than the rate of translocation determined for the Mr = 45,000-47,000 transporter in L1210 cells. During induced maturation of HL-60/LCV cells toward the granulocyte pathway, [3H]methotrexate (MTX) influx capacity and the amount of the affinity labeled transporter decreased rapidly in a parallel fashion. The decrease in [3H]MTX influx and in affinity labeling and in the amount of the Mr = 75,000-80,000 transporter was 5-fold following exposure to 210 mM dimethyl sulfoxide (Me2SO) for 5 days during growth in culture. Moreover, during cycloheximide treatment, the decay in [3H]MTX influx at 37 degrees C and in amount of affinity labeled transporter was the same (t1/2 = 144-155 min) for both control and Me2SO-treated HL-60/LCV cells. These results, which reveal no difference in metabolic turnover for control and Me2SO-treated cells, suggest that the decline in folate analogue influx in HL-60/LCV influx cells is a very early event in the program of differentiation and probably occurs by down-regulation of synthesis of the transporter for the one-carbon reduced-folate transport system. 相似文献
880.