全文获取类型
收费全文 | 926篇 |
免费 | 78篇 |
出版年
2023年 | 12篇 |
2022年 | 17篇 |
2021年 | 27篇 |
2020年 | 9篇 |
2019年 | 17篇 |
2018年 | 11篇 |
2017年 | 14篇 |
2016年 | 31篇 |
2015年 | 43篇 |
2014年 | 50篇 |
2013年 | 69篇 |
2012年 | 75篇 |
2011年 | 75篇 |
2010年 | 47篇 |
2009年 | 42篇 |
2008年 | 52篇 |
2007年 | 34篇 |
2006年 | 42篇 |
2005年 | 46篇 |
2004年 | 34篇 |
2003年 | 40篇 |
2002年 | 37篇 |
2001年 | 14篇 |
2000年 | 18篇 |
1999年 | 11篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1979年 | 3篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 4篇 |
1969年 | 6篇 |
1968年 | 4篇 |
排序方式: 共有1004条查询结果,搜索用时 15 毫秒
1.
Zhaolin Wang Cara Fraley Adam R. Mezo 《Bioorganic & medicinal chemistry letters》2013,23(5):1253-1256
The neonatal Fc receptor, FcRn, prolongs the half-life of IgG in the serum and represents a potential therapeutic target for the treatment of autoimmune disease. Small molecules that block the protein–protein interactions of human IgG–human FcRn may lower pathogenic autoantibodies and provide effective treatment. A novel class of quinoxalines has been discovered as antagonists of the IgG:FcRn protein–protein interaction through optimization of a hit derived from a virtual ligand-based screen. 相似文献
2.
3.
Thermal sensitivity of scope for activity in Pagothenia borchgrevinki, a cryopelagic Antarctic nototheniid fish 总被引:1,自引:1,他引:0
The thermal sensitivity of scope for activity was studied in the Antarctic nototheniid fish Pagothenia borchgrevinki. The scope for activity of P. borchgrevinki at 0°C was 189 mg O2 kg−1 h−1 (factorial scope 6.8) which is similar to that of temperate and tropical species at their environmental temperatures, providing no evidence for metabolic cold adaptation of maximum activity. The scope for activity increased to a maximum value of 266 mg O2 kg−1 h−1 (factorial scope 8.3) at 3°C and then decreased from 3 to 6°C. The thermal sensitivity of critical swimming speed was also investigated and followed a similar pattern to aerobic scope for activity, suggesting oxygen limitation of aerobic performance. Oxygen consumption rates and ventilation frequencies were monitored for 24 h after the swimming challenge and the recovery of both parameters to resting levels was rapid and independent of temperature. 相似文献
4.
Proteolytically modified human beta 2-microglobulin augments the specific cytotoxic activity in murine mixed lymphocyte culture 总被引:1,自引:0,他引:1
A proteolytically modified form of beta 2-microglobulin (beta 2-m) present in the serum of patients suffering from autoimmune, immunodeficient diseases and cancer has been reported in the literature. In the present study we show that human beta 2-m as well as the proteolytically modified human form (M-beta 2-m) bind to murine lymphocytes expressing H-2 class I antigens; M-beta 2-m, when added at day 0 and 1 of culture in nanomolar concentrations to a one-way murine allogeneic mixed lymphocyte culture (MLC) augments the generation of specific cytotoxic T lymphocytes; M-beta 2-m increases the endogenous production of interleukin 2 in the MLC culture; monoclonal antibody which reacts with both the native beta 2-m and M-beta 2-m molecule blocks the augmentation of cytotoxic T lymphocyte production induced by M-beta 2-m; murine as well as human MLC responder cells can proteolytically modify native human beta 2-m; and the modifying activity of murine MLC responder cells was blocked in an intermediary step by an alloantibody, which reacts specifically with murine major histocompatibility complex, class I-associated beta 2-m. These findings suggest that the modification process is preceded by an association of human beta 2-m with the cell surface of the responder cells. Our data indicate that the modification of beta 2-m might reflect early events in allospecific responder cell activation. 相似文献
5.
A modified form of beta-2-microglobulin (beta-2-m) has previously been described to be present in serum from patients suffering from autoimmune diseases, acquired immune deficiency syndrome and small-cell lung cancer [Plesner, T. and Wiik, A. (1979) Scand. J. Immunol. 9, 247-254; Bhalla et al. (1985) Clin. Chem. 31, 1411-1412; Nissen et al. (1984) Clin. Chim. Acta 141, 41-50]. In the present study we describe the purification and characterization of this modified human serum beta-2-m from patients with small-cell lung cancer. Purified urinary beta-2-m was added to the serum samples incubated at 20 degrees C for five days to obtain a higher yield of modified beta-2-m (m-beta-2-m). m-beta-2-m was then purified from serum by gel filtration followed by chromatofocusing of the fractions containing beta-2-m. m-beta-2-m was found to have an apparent molecular mass of 15 kDa and a pI of 5.3 when analyzed by sodium dodecyl sulphate/polyacrylamide gel electrophoresis and analytical isoelectric focusing respectively. Amino acid analysis of m-beta-2-m revealed that the protein is missing one lysine residue compared to the composition deduced from the cDNA sequence of beta-2-m. Amino acid sequence analysis showed that m-beta-2-m consists of two polypeptide chains produced by a proteolytic cleavage of beta-2-m in the disulphide loop. After reduction and alkylation of m-beta-2-m the two chains were separated by reverse-phase high-pressure liquid chromatography. By amino acid sequencing, amino acid residues 1-56 and 59-99 were identified in the A and B chains respectively. By comparison of the amino acid composition of m-beta-2-m with the known sequence of beta-2-m it was possible to deduce the existence of a Ser-57 in the A chain. Thus proteolytic cleavage of beta-2-m in the intrachain disulphide loop releases the amino acid Lys-58, which results in a modified form of beta-2-m with a molecular mass of 11,620 Da as determined by amino acid analysis. 相似文献
6.
Dose responses of gibberellins 总被引:4,自引:0,他引:4
Per Nissen 《Physiologia plantarum》1988,72(1):197-203
To determine the response type, published data for the most widely used bioassays for gibberellins have been analyzed by means of a computer program for estimating sensitivity parameters, or by interpolation. The dose response data are almost uniformly subsensitive, i. e. more than an 81-fold increase in external gibberellin concentration is required for a change from 10 to 90% of maximal response (S90 /S10 ). Data for the interaction of gibberellins with artificial membranes are, in contrast, markedly ultrasensitive (S90 /S10 ± 10). This difference further strengthens the view that lipid structures do not function as receptors for gibberellins. Most of the subsensitive dose responses for gibberellins can be quite precisely represented by cooperative isotherms. However, available data are insufficiently detailed for an unequivocal choice among cooperative, multiphasic or more complex kinetics. 相似文献
7.
Varda Mann Ilana Ekstein Hilde Nissen Carrie Hiser Lee Mclntosh Joseph Hirschberg 《Plant molecular biology》1991,17(3):559-566
We have cloned and analyzed the sugar-beet mitochondrial gene for cytochrome oxidase subunit II (coxII). The sugar-beet and its deduced amino acid sequence were compared to its homologouscoxII gene sequences from both monocot and dicot plants. It was found to be highly conserved (89–95%) compared to homologue in other plant species. The 780 bp coding sequence of the sugar beetcoxII gene is interrupted at position 383 by a 1463 bp intron. This intron contains an additional 107 bp sequence that is not found in any of the plantcoxII genes studied thus far. The structure of the intron suggests that a large intron existed in an ancestralcoxII gene before monocots and dicots diverged in evolution. Three CGG codons in the sugar-beetcoxII coding sequence align with conserved tryptophan residues in the homologous gene of other species, suggesting that RNA editing takes place also in sugar-beet mitochondria. In 13 out of 24 codons ofcoxII mRNA that were found to be edited in four other plants, the sugar-beet gene already utilizes the edited codons. This phenomenon may indicate that the mitochondrial genome in sugar-beet is phylogenetically more archaic relative to these plants. An additional sequence of 279 bp that is identical to the first exon ofcoxII was identified in the mtDNA of the sugar-beet. This pseudo-gene is transcribed and its existence in the mitochondrial genome is unexplained. 相似文献
8.
The chemically induced barley (Hordeum vulgare L.) mutation, agr, was found to be a simple recessive trait resulting in agravitropic roots and normal gravitropic shoots. The total seedling root growth was similar for mutant and wild-type roots, although the mutant had fewer roots per seed and greater elongation per root. Although the concentration of exogenous indole-3-acetic acid (IAA) required to reduce root growth by 50% (GR50) was 12 times greater for the agravitropic mutant, agravitropic and gravitropic roots were equally sensitive to exogenous applications of 2,4-dichlorophenoxyacetic acid (2,4-D) and naphthalene acetic acid (NAA). Root IAA contents, determined by high-pressure liquid chromatography (HPLC), were not different for gravitropes and agravitropes. The greater root elongation rates, lack of sensitivity to exogenous IAA, and normal endogenous IAA levels indicate that auxin-controlled growth regulation may be altered in the mutant. 相似文献
9.
J. A. Magnuson E. R. Pandolfino G. R. Munske A. E. Namen M. S. Nissen 《Journal of biosciences》1983,5(1):83-91
Two lectins, a tetramer designated LBL4 and an octamer LBL8 designated have been purified from the lima beanPhaseolus lunatus. The tetramer appears to be nonmitogenic for human lymphocytes and is a weak mitogen for bovine cells. The octamer and a chemically cross-linked form of the tetramer are good mitogens. The lima bean lectin binds to only certain sub-populations of human lymphocytes. The primary class which does not bind appears to be a sub-population ofT-lymphocytes. Comparisons of cell binding with other lectins which bind to 2-acetamido-2-deoxy-D-galactose have been carried out. Quantitative analysis of the binding to human erythrocytes is co-operative but binding to lymphocytes is non-co-operative. These results show that there may not be a direct correlation between mitogenic stimulation and cooperative binding to membrane receptors. 相似文献
10.
Cysteamine (2-aminoethanethiol) inhibited cell division in synchronously dividing cultures of Euglena gracilis at relatively low concentrations (0.005 M), Cystamine (2,2′-dithiobis(ethylamine). however, was only partially inhibitory at high concentrations (0.1 M). This differential inhibition may reflect certain unique features of nuclear division in euglenoid flagellates. 相似文献