全文获取类型
收费全文 | 147篇 |
免费 | 17篇 |
出版年
2023年 | 1篇 |
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 12篇 |
2014年 | 5篇 |
2013年 | 7篇 |
2012年 | 13篇 |
2011年 | 5篇 |
2010年 | 9篇 |
2009年 | 4篇 |
2008年 | 8篇 |
2007年 | 5篇 |
2006年 | 5篇 |
2005年 | 7篇 |
2004年 | 4篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 2篇 |
1964年 | 1篇 |
1962年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有164条查询结果,搜索用时 62 毫秒
1.
The Saccharomyces cerevisiae CKS1 gene, a homolog of the Schizosaccharomyces pombe suc1+ gene, encodes a subunit of the Cdc28 protein kinase complex. 总被引:22,自引:7,他引:15
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J A Hadwiger C Wittenberg M D Mendenhall S I Reed 《Molecular and cellular biology》1989,9(5):2034-2041
The Saccharomyces cerevisiae gene CDC28 encodes a protein kinase required for cell cycle initiation. In an attempt to identify genes encoding proteins that interact with the Cdc28 protein kinase, high-copy plasmid suppressors of a temperature-sensitive cdc28 mutation were isolated. One such suppressor, CKS1, was found to encode an 18-kilodalton protein that shared a high degree of homology with the suc1+ protein (p13) of Schizosaccharomyces pombe (67% amino acid sequence identity). Disruption of the chromosomal CKS1 gene conferred a G1 arrest phenotype similar to that of cdc28 mutants. The presence of the 18-kilodalton Cks1 protein in yeast lysates was demonstrated by using Cks-1 specific antiserum. Furthermore, the Cks1 protein was shown to be physically associated with active forms of the Cdc28 protein kinase. These data suggest that Cks1 is an essential component of the Cdc28 protein kinase complex. 相似文献
2.
C L Mendenhall C J Grossman G A Roselle Z Hertelendy S J Ghosn K Lamping K Martin 《The Journal of steroid biochemistry and molecular biology》1990,37(1):71-76
As an untoward effect of chronic anabolic steroid use, immunologic alterations may be induced. To evaluate this possibility five commercially available steroids with various types of structural differences were studied in male Sprague-Dawley rats. Animals were divided into five groups and treated with testosterone (Group 1), testosterone propionate (Group 2), testolactone (Group 3), oxandrolone (Group 4), and stanozolol (Group 5). Androgenic anabolic steroids were administered daily, subcutaneously dissolved in oil, at a dose of 1.1 mg/kg. Immune alterations were assessed by skin-test responses to phytohemagglutinin. After five days of treatment (1.1 mg/kg/day) a significant immuno-suppression was observed with all groups. However, by day 10, groups 3, 4, and 5 showed an immuno-stimulation. Using oxandrolone as the model stimulant, serum testosterone levels were significantly suppressed, while castration abolished the stimulatory effect. These observations indicate that immune alterations do occur with anabolic steroids which are immuno-suppressive when the steroid nucleus is intact and immuno-stimulatory with nuclear alterations. It appears that these changes are associated with altered gonadal testosterone release. 相似文献
3.
4.
5.
6.
At high viable cell concentrations in large-scale mammalian cell culture processes, the accumulation of dissolved carbon dioxide (dCO(2), typically quantified as an equilibrium gas-phase concentration) becomes problematic as a result of low CO(2) removal rates at reduced surface-to-volume ratios. High dCO(2) concentrations have previously been shown to inhibit cell growth and product formation in mammalian cells and to alter the glycosylation pattern of recombinant proteins. Therefore, reliable monitoring and control of dCO(2) are important for successful large-scale operation. Off-line measurements by instruments such as blood gas analyzers (BGA) are constrained by the low frequency of data collection and cannot be used for on-line control. In a preliminary evaluation of the YSI 8500 in situ sensor, a response time (t(90%)) of 6 min, sensitivity of 0.5% CO(2) (3.6 mmHg), and linearity of measurement (R(2) = 0.9997) between the equivalent gas-phase partial pressure of 0-180 mmHg (0% and 25% CO(2)) were established. Measurements were found to be unaffected by culture pH and typical mammalian cell culture concentrations of glucose, glutamine, glutamate, lactate, and ammonium. The sensor withstood repeated sterilization and cleaning cycles. The reliability of this sensor was demonstrated in microcarrier-based Chinese hamster ovary (CHO) cell perfusion cultures at reactor scales of 30, 40, 340, and 2000 L and was successfully implemented in a dCO(2) control strategy using N(2) sparging. 相似文献
7.
Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献8.
Intervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune
diseases. A new report by Schurgers and colleagues in a previous issue of Arthritis Research & Therapy sheds novel mechanistic insight into the pathways employed by MSCs to suppress T-cell proliferation in vitro, but, at the same time, indicates that MSCs do not influence T-cell reactivity and the disease course in an in vivo arthritis model. Such discrepancies between the in vitro and in vivo effects of potent cellular immune modulators should spark further research and should be interpreted as a sign of caution
for the in vitro design of MSC-derived interventions in the setting of human autoimmune diseases. 相似文献
9.
Bahareh Honarparvar Sachin A Pawar Cláudio Nahum Alves Jer?nimo Lameira Glenn EM Maguire José Rogério A Silva Thavendran Govender Hendrik G Kruger 《Journal of biomedical science》2015,22(1)
Background
Novel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC50 values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC50) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.Results
The PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC50 = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC50 = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆Gsolv) were also considered.Conclusions
A general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC50 data.Electronic supplementary material
The online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users. 相似文献10.
Nadine Kraemer Ethiraj Ravindran Sami Zaqout Gerda Neubert Detlev Schindler Olaf Ninnemann Ralph Gr?f Andrea EM Seiler Angela M Kaindl 《Cell cycle (Georgetown, Tex.)》2015,14(13):2044-2057
Biallelic mutations in the gene encoding centrosomal CDK5RAP2 lead to autosomal recessive primary microcephaly (MCPH), a disorder characterized by pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. The current model for the microcephaly phenotype in MCPH invokes a premature shift from symmetric to asymmetric neural progenitor-cell divisions with a subsequent depletion of the progenitor pool. The isolated neural phenotype, despite the ubiquitous expression of CDK5RAP2, and reports of progressive microcephaly in individual MCPH cases prompted us to investigate neural and non-neural differentiation of Cdk5rap2-depleted and control murine embryonic stem cells (mESC). We demonstrate an accumulating proliferation defect of neurally differentiating Cdk5rap2-depleted mESC and cell death of proliferative and early postmitotic cells. A similar effect does not occur in non-neural differentiation into beating cardiomyocytes, which is in line with the lack of non-central nervous system features in MCPH patients. Our data suggest that MCPH is not only caused by premature differentiation of progenitors, but also by reduced propagation and survival of neural progenitors. 相似文献