全文获取类型
收费全文 | 1509篇 |
免费 | 124篇 |
出版年
2021年 | 21篇 |
2020年 | 12篇 |
2019年 | 14篇 |
2018年 | 16篇 |
2017年 | 21篇 |
2016年 | 29篇 |
2015年 | 41篇 |
2014年 | 44篇 |
2013年 | 63篇 |
2012年 | 83篇 |
2011年 | 66篇 |
2010年 | 44篇 |
2009年 | 56篇 |
2008年 | 69篇 |
2007年 | 68篇 |
2006年 | 59篇 |
2005年 | 60篇 |
2004年 | 71篇 |
2003年 | 70篇 |
2002年 | 61篇 |
2001年 | 58篇 |
2000年 | 65篇 |
1999年 | 43篇 |
1998年 | 29篇 |
1997年 | 16篇 |
1996年 | 26篇 |
1995年 | 12篇 |
1994年 | 14篇 |
1993年 | 26篇 |
1992年 | 21篇 |
1991年 | 15篇 |
1990年 | 24篇 |
1989年 | 22篇 |
1988年 | 27篇 |
1987年 | 19篇 |
1986年 | 14篇 |
1985年 | 20篇 |
1984年 | 14篇 |
1983年 | 15篇 |
1982年 | 14篇 |
1980年 | 11篇 |
1979年 | 12篇 |
1978年 | 14篇 |
1976年 | 10篇 |
1975年 | 11篇 |
1974年 | 20篇 |
1973年 | 10篇 |
1972年 | 18篇 |
1971年 | 12篇 |
1966年 | 7篇 |
排序方式: 共有1633条查询结果,搜索用时 15 毫秒
931.
Schulz BL Sloane AJ Robinson LJ Prasad SS Lindner RA Robinson M Bye PT Nielson DW Harry JL Packer NH Karlsson NG 《Glycobiology》2007,17(7):698-712
Cystic fibrosis (CF) is characterized by chronic lung infection and inflammation, with periods of acute exacerbation causing severe and irreversible lung tissue damage. We used protein and glycosylation analysis of high-molecular mass proteins in saline-induced sputum from CF adults with and without an acute exacerbation, CF children with stable disease and preserved lung function, and healthy non-CF adult and child controls to identify potential biomarkers of lung condition. While the main high-molecular mass proteins in the sputum from all subjects were the mucins MUC5B and MUC5AC, these appeared degraded in CF adults with an exacerbation. The glycosylation of these mucins also showed reduced sulfation, increased sialylation, and reduced fucosylation in CF adults compared with controls. Despite improvements in pulmonary function after hospitalization, these differences remained. Two CF children showed glycoprotein profiles similar to those of CF adults with exacerbations and also presented with pulmonary flares shortly after sampling, while the remaining CF children had profiles indistinguishable from those of healthy non-CF controls. Sputum mucin glycosylation and degradation are therefore not inherently different in CF, and may also be useful predictive biomarkers of lung condition. 相似文献
932.
Activation of cyclin B1–cyclin-dependent kinase 1 (Cdk1), triggered by a positive feedback loop at the end of G2, is the key event that initiates mitotic entry. In metaphase, anaphase-promoting complex/cyclosome–dependent destruction of cyclin B1 inactivates Cdk1 again, allowing mitotic exit and cell division. Several models describe Cdk1 activation kinetics in mitosis, but experimental data on how the activation proceeds in mitotic cells have largely been lacking. We use a novel approach to determine the temporal development of cyclin B1–Cdk1 activity in single cells. By quantifying both dephosphorylation of Cdk1 and phosphorylation of the Cdk1 target anaphase-promoting complex/cyclosome 3, we disclose how cyclin B1–Cdk1 continues to be activated after centrosome separation. Importantly, we discovered that cytoplasmic cyclin B1–Cdk1 activity can be maintained even when cyclin B1 translocates to the nucleus in prophase. These experimental data are fitted into a model describing cyclin B1–Cdk1 activation in human cells, revealing a striking resemblance to a bistable circuit. In line with the observed kinetics, cyclin B1–Cdk1 levels required to enter mitosis are lower than the amount of cyclin B1–Cdk1 needed for mitotic progression. We propose that gradually increasing cyclin B1–Cdk1 activity after centrosome separation is critical to coordinate mitotic progression. 相似文献
933.
Fused silica-packed capillary columns containing vancomycin immobilized by reductive amination on an aldehyde-silica were used to separate enantiomers of some non-steroidal anti-inflammatory drugs. Attempts have been made to qualitatively explain the influence of various mobile phase compositions on the enantioselective retention. The effects of mobile phase pH, buffer, and organic modifier concentrations were investigated as well as the influence of salts of hydrophobic ions added to the mobile phase to induce ion pair retention. Chirality 10:273–280, 1998. © 1998 Wiley-Liss, Inc. 相似文献
934.
Beta 2-microglobulin-deficient background ameliorates lethal phenotype of the TGF-beta 1 null mouse.
S Kobayashi K Yoshida J M Ward J J Letterio G Longenecker L Yaswen B Mittleman E Mozes A B Roberts S Karlsson A B Kulkarni 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(7):4013-4019
TGF-beta 1 null (TGF-beta1-/-) mice die at 3-4 wk of age and show an autoimmune inflammatory phenotype associated with enhanced expression of both class I and II MHC molecules. To determine the role of MHC class I Ags in the autoimmune manifestations and the inflammation observed in TGF-beta 1-/- mice, we generated TGF-beta 1-/- mice in the genetic background of beta 2-microglobulin deficiency (beta 2M-/-). TGF-beta 1-/-;beta 2M-/- mice had improved survival compared with TGF-beta 1-/- mice. Histopathological examination showed less severe inflammation, especially in the heart, where Mac-2 reactive macrophages were significantly decreased as compared with TGF-beta 1-/- mice. In vivo depletion of CD8+ T cells in TGF-beta 1-/- mice confirmed suppression of inflammation and reduction in the severity of the wasting syndrome. MHC class II mRNA expression in TGF-beta 1-/-;beta 2M-/- mice was also lower than that in TGF-beta 1-/- mice, suggesting reduced systemic inflammation. Autoimmune response as judged by serum Ab titers to ssDNA and 16/6 Id and by immune complex deposits in kidney was reduced in TGF-beta 1-/-;beta 2M-/- mice, when compared with that in TGF-beta 1-/- mice. Our data thus indicate that MHC class I molecules influence the development of the autoimmunity and the inflammation seen in TGF-beta 1-/- mice and CD8+ T cells may have a contribution to the inflammation in TGF-beta 1-/- mice. 相似文献
935.
H Schüler E Korenbaum C E Schutt U Lindberg R Karlsson 《European journal of biochemistry》1999,265(1):210-220
This paper compares wild-type and two mutant beta-actins, one in which Ser14 was replaced by a cysteine, and a second in which both Ser14 and Asp157 were exchanged (Ser14-->Cys and Ser14-->Cys, Asp157-->Ala, respectively). Both of these residues are part of invariant sequences in the loops, which bind the ATP phosphates, in the interdomain cleft of actin. The increased nucleotide exchange rate, and the decreased thermal stability and affinity for DNase I seen with the mutant actins indicated that the mutations disturbed the interdomain coupling. Despite this, the two mutant actins retained their ATPase activity. In fact, the mutated actins expressed a significant ATPase activity even in the presence of Ca2+ ions, conditions under which actin normally has a very low ATPase activity. In the presence of Mg2+ ions, the ATPase activity of actin was decreased slightly by the mutations. The mutant actins polymerized as the wild-type protein in the presence of Mg2+ ions, but slower than the wild-type in a K+/Ca2+ milieu. Profilin affected the lag phases and elongation rates during polymerization of the mutant and wild-type actins to the same extent, whereas at steady-state, the concentration of unpolymerized mutant actin appeared to be elevated. Decoration of mutant actin filaments with myosin subfragment 1 appeared to be normal, as did their movement in the low-load motility assay system. Our results show that Ser14 and Asp157 are key residues for interdomain communication, and that hydroxyl and carboxyl groups in positions 14 and 157, respectively, are not necessary for ATP hydrolysis in actin. 相似文献
936.
The structure of the pneumococcal common antigen, C-polysaccharide, from a noncapsulated pneumococcal strain, CSR SCS2, was studied using 1H-NMR, 13C-NMR and 31P-NMR spectroscopy. The dependence of NMR chemical shifts on the variation in pD was also studied. It was established that the C-polysaccharide is composed of a backbone of tetrasaccharide-ribitol repeating units that are linked to each other by a phosphodiester linkage between position 5 of a D-ribitol residue and position 6 of a beta-D-glucopyranosyl residue. The polysaccharide is substituted with one residue of phosphocholine at position 6 of the 4-substituted 2-acetamido-2-deoxy-alpha-D-galactopyranosyl residue. Both galactosamine residues in the polysaccharide are N-acetylated. O)-P-Cho | 6 6)-beta-D-Glcp-(1-->3)-alpha-AATp-(1-->4)-alpha-D-GalpNAc-(1-->3)- bet a-D-GalpNAc-(1-->1)-D-ribitol-5-P-(O--> where AAT is 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose and Cho is choline. This structure differs, concerning phosphocholine substituents and N-acetylation, from those reported previously for pneumococcal C-polysaccharide [Jennings, H.J., Lugowski, C. & Young, N.M. (1980) Biochemistry 19, 4712-4719; Fischer, W., Behr, T., Hartmann, R., Peter-Katalinic, J. & Egge, H. (1993) Eur. J. Biochem. 215, 851-857; Kulakowska, M., Brisson, J.-R., Griffith, D.W., Young, N.M. & Jennings, H.J. (1993) Can. J. Chem. 71, 644-648]. The structures of the C-polysaccharides present in three pneumococcal types were also examined. They contain one (in 18B) or two (in 32F and 32A) phosphocholine residues in the repeating unit. The degree of substitution was not determined. The backbone of all examined C-polysaccharides was identical and in all cases both galactosamine residues appeared to be N-acetylated. 相似文献
937.
Reappearance of Founder Virus Sequence in Human Immunodeficiency Virus Type 1-Infected Patients 总被引:1,自引:0,他引:1 下载免费PDF全文
Annika C. Karlsson Hans Gaines Matti Sllberg Stefan Lindbck Anders Snnerborg 《Journal of virology》1999,73(7):6191-6196
Different patterns of temporal evolution in human immunodeficiency virus type 1 V3 and p17 regions are described for eight patients studied during the first years following primary infection. In samples from three patients, a rapid replacement of the major sequence occurred but the original sequence reappeared later simultaneously with clinical deterioration and increased plasma viral load. 相似文献
938.
HDAC4 deacetylase associates with and represses the MEF2 transcription factor. 总被引:28,自引:0,他引:28 下载免费PDF全文
E A Miska C Karlsson E Langley S J Nielsen J Pines T Kouzarides 《The EMBO journal》1999,18(18):5099-5107
939.
M. Abou-hachem F. Olsson M. P. Williamson S. Linse S. J. Crennell G. O. Hreggvidsson J. K. Kristjansson O. Holst E. Nordberg Karlsson 《Biocatalysis and Biotransformation》1999,21(4):253-260
The thermophilic marine bacterium Rhodothermus marinus produces a modular family 10 xylanase (Xyn10A). It consists of two N-terminal family 4 carbohydrate binding modules (CBMs) followed by a domain of unknown function (D3), and a catalytic module (CM) flanked by a small fifth domain (D5) at its C-terminus. Several truncated mutants of the enzyme have been produced and characterised with respect to biochemical properties and stability. Multiple calcium binding sites are shown to be present in the two N-terminal CBMs and recent evidence suggests that the third domain of the enzyme also has the ability to bind the same metal ligand. The specific binding of Ca2+ was demonstrated to have a pronounced effect on thermostability as shown by differential scanning calorimetry and thermal inactivation studies. Furthermore, deletion mutants of the enzyme were less stable than the full-length enzyme suggesting that module interactions contributed to the stability of the enzyme. Finally, recent evidence indicates that the fifth domain of Xyn10A is a novel type of module mediating cell-attachment. 相似文献
940.