全文获取类型
收费全文 | 1355篇 |
免费 | 26篇 |
国内免费 | 22篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 8篇 |
2020年 | 12篇 |
2019年 | 18篇 |
2018年 | 22篇 |
2017年 | 8篇 |
2016年 | 20篇 |
2015年 | 14篇 |
2014年 | 47篇 |
2013年 | 58篇 |
2012年 | 25篇 |
2011年 | 53篇 |
2010年 | 29篇 |
2009年 | 42篇 |
2008年 | 29篇 |
2007年 | 48篇 |
2006年 | 48篇 |
2005年 | 44篇 |
2004年 | 40篇 |
2003年 | 43篇 |
2002年 | 37篇 |
2001年 | 29篇 |
2000年 | 18篇 |
1999年 | 25篇 |
1998年 | 39篇 |
1997年 | 49篇 |
1996年 | 32篇 |
1995年 | 25篇 |
1994年 | 38篇 |
1993年 | 35篇 |
1992年 | 34篇 |
1991年 | 29篇 |
1990年 | 44篇 |
1989年 | 30篇 |
1988年 | 40篇 |
1987年 | 23篇 |
1986年 | 42篇 |
1985年 | 33篇 |
1984年 | 40篇 |
1983年 | 21篇 |
1982年 | 27篇 |
1981年 | 26篇 |
1980年 | 19篇 |
1979年 | 16篇 |
1978年 | 11篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1975年 | 4篇 |
1973年 | 2篇 |
排序方式: 共有1403条查询结果,搜索用时 15 毫秒
101.
The present work describes a very simple technique for the isolation within 2-3 hr of inactive phosphoenolpyruvate carboxylase protein starting from a crude extract of Sorghum leaves by using an immunoadsorbent column prepared with a glutaraldehyde- activated gel. The conditions for the total elution of the enzyme protein are optimized. For quantitative determinations cyanogen bromide-activated gels should be avoided as the release of fixed immunoglobulin G (IgG) has been observed during washing with the acidic buffer needed to elute the enzyme. In that respect, glutaraldehyde-activated gel does not lose antibodies and consequently gives accurate results. 相似文献
102.
Neijssel O. M. Hardy G. P. M. A. Lansbergen J. C. Tempest D. W. O'Brien R. W. 《Archives of microbiology》1980,125(1-2):175-179
A consistent difference was found between glucose-limited cultures of Escherichia coli and Klebsiella aerogenes strains in the manner which their apparent cellular content of glucose: phosphoenolpyruvate phosphotransferase (glucose-PTS) varied with growth rate. With the former strains, activity increased as a function of growth rate; in the latter it decreased. However, under glucose-sufficient conditions (potassium-or ammonia-limitation) both species behaved similarly; the glucose-PTS activity was lower and bore no obvious relationship to the rate of glucose consumption expressed by the growing culture. These results are discussed in relation to the role of glucose as a regulator of glucose-PTS synthesis, and to the likely contribution which the glucose-PTS makes to the overall rate of glucose uptake, particularly by cells growing in glucose-sufficient environments.Abbreviation Glucose-PTS
phosphoenolpyruvate phosphotransferase
From May to November 1978 on study leave in the University of Amsterdam 相似文献
103.
104.
We have examined genetic complementation in pyruvate carboxylase deficiency by comparing the enzyme activity in polyethylene glycol-induced heterokaryons with that in unfused mixtures of fibroblasts from three affected children. Complementation, manifested as a three- to sevenfold increase in pyruvate carboxylase activity, was observed in fusions between a biotin-responsive multiple carboxylase (pyruvate carboxylase, propionyl CoA carboxylase, and -methylcrotonyl CoA carboxylase) deficient fibroblast line and two other lines deficient only in pyruvate carboxylase activity. Kinetic analysis of complementing pyruvate carboxylase deficient lines, measured by the rate of restoration of enzyme activity as a function of time, revealed that maximum restoration was achieved within 10–24 hr after fusion. This profile is similar to those observed for fusions between the multiple carboxylase deficient line and two lines deficient in propionyl CoA carboxylase activity that are known to represent different gene mutations. Although the patients with pyruvate carboxylase deficiency had similar clinical findings, our studies indicate that pyruvate carboxylase deficiency is genetically heterogeneous, with at least two distinct, probably intergenic, complementation groups.This work was supported by an NIH research grant (AM 25675) and an A. D. Williams research grant (6-48360). B. Wolf is the recipient of an NIH Research Career Development Award (AM 00677) and is aided by a Basil O'Connor Starter Research Grant from The National Foundation-March of Dimes (5-263). G. Feldman is the recipient of an NIH predoctoral training grant (GM 07492). This article is No. 100 from the Department of Human Genetics at the Medical College of Virginia. 相似文献
105.
In Acetobacter aceti growing on pyruvate as the only source of carbon and energy, oxaloacetate (OAA) is produced by a phosphoenolpyruvate (PEP) carboxylase (EC 4.1.1.31). The enzyme was purified 122-fold and a molecular weight of about 380,000 was estimated by gel filtration.The optimum pH was 7.5 and the K
m
values for PEP and NaHCO3 were 0.49 mM and about 3 mM, respectively. The enzyme needed a divalent cation; the K
m
for Mn2+, Co2+ and Mg2+ were 0.12, 0.26 and 0.77 mM, respectively. Maximal activity was only obtained with Mg2+. Mn2+ and Co2+ became inhibitory at high concentrations.The activity was inhibited by succinate and, to a lesser extent, by fumarate, citrate, -ketoglutarate, aspartate and glutamate.As compared with the corresponding enzyme from A. xylinum, the PEP carboxylase of A. aceti showed the following differences: a) It had an absolute requirement for acetyl CoA (K
a
0.18 mM) or propionyl CoA (K
a
0.2 mM). b) It was not affected by ADP. c) It was sensitive to thiol blocking agents.Abbreviations PEP
phosphoenolpyruvate
- OAA
oxaloacetate
- MW
molecular weight
- TEMG buffer
50 mM Tris-HCl, pH 7.5, 1 mM EDTA, 5 mM MgCl2, 1 mM glutathione
- HEPES
N-2-hydroxyethylpiperazine-N-ethanesulfonic acid 相似文献
106.
Federico Machinandiarena Leandro Nakamatsu Gustavo E. Schujman Diego de Mendoza Daniela Albanesi 《Molecular microbiology》2020,114(4):653-663
A key aspect in membrane biogenesis is the coordination of fatty acid to phospholipid synthesis rates. In most bacteria, PlsX is the first enzyme of the phosphatidic acid synthesis pathway, the common precursor of all phospholipids. Previously, we proposed that PlsX is a key regulatory point that synchronizes the fatty acid synthase II with phospholipid synthesis in Bacillus subtilis. However, understanding the basis of such coordination mechanism remained a challenge in Gram-positive bacteria. Here, we show that the inhibition of fatty acid and phospholipid synthesis caused by PlsX depletion leads to the accumulation of long-chain acyl-ACPs, the end products of the fatty acid synthase II. Hydrolysis of the acyl-ACP pool by heterologous expression of a cytosolic thioesterase relieves the inhibition of fatty acid synthesis, indicating that acyl-ACPs are feedback inhibitors of this metabolic route. Unexpectedly, inactivation of PlsX triggers a large increase of malonyl-CoA leading to induction of the fap regulon. This finding discards the hypothesis, proposed for B. subtilis and extended to other Gram-positive bacteria, that acyl-ACPs are feedback inhibitors of the acetyl-CoA carboxylase. Finally, we propose that the continuous production of malonyl-CoA during phospholipid synthesis inhibition provides an additional mechanism for fine-tuning the coupling between phospholipid and fatty acid production in bacteria with FapR regulation. 相似文献
107.
Impaired G2/M cell cycle arrest induces apoptosis in pyruvate carboxylase knockdown MDA-MB-231 cells
Khanti Rattanapornsompong Janya Khattiya Phatchariya Phannasil Narumon Phaonakrop Sittiruk Roytrakul Sarawut Jitrapakdee Chareeporn Akekawatchai 《Biochemistry and Biophysics Reports》2021
BackgroundPrevious studies showed that suppression of pyruvate carboxylase (PC) expression in highly invasive breast cancer cell line, MDA-MB-231 inhibits cell growth as a consequence of the impaired cellular biosynthesis. However, the precise cellular mechanism underlying this growth restriction is unknown.MethodsWe generated the PC knockdown (PCKD) MDA-MB-231 cells and assessed their phenotypic changes by fluorescence microscopy, proliferation, apoptotic, cell cycle assays and proteomics.ResultsPC knockdown MDA-MB-231 cells had a low percentage of cell viability in association with accumulation of abnormal cells with large or multi-nuclei. Flow cytometric analysis of annexin V-7-AAD positive cells showed that depletion of PC expression triggers apoptosis with the highest rate at day 4. The increased rate of apoptosis is consistent with increased cleavage of procaspase 3 and poly (ADP-Ribose) polymerase. Cell cycle analysis showed that the apoptotic cell death was associated with G2/M arrest, in parallel with marked reduction of cyclin B levels. Proteomic analysis of PCKD cells identified 9 proteins whose expression changes were correlated with the degree of apoptosis and G2/M cell cycle arrest in the PCKD cells. STITCH analysis indicated 3 of 9 candidate proteins, CCT3, CABIN1 and HECTD3, that form interactions with apoptotic and cell cycle signaling networks linking to PC via MgATP.ConclusionsSuppression of PC in MDA-MB-231 cells induces G2/M arrest, leading to apoptosis. Proteomic analysis supports the potential involvement of PC expression in the aberrant cell cycle and apoptosis, and identifies candidate proteins responsible for the PC-mediated cell cycle arrest and apoptosis in breast cancer cells.General significanceOur results highlight the possibility of the use of PC as an anti-cancer drug target. 相似文献
108.
A Single Nucleotide Polymorphism of Chicken Acetyl-CoA Carboxylase A Gene Associated with Fatness Traits 总被引:1,自引:0,他引:1
Acetyl-CoA carboxylase α (ACCα) is a major rate-limiting enzyme in the biogenesis of long-chain fatty acids. It can catalyze the carboxylation of acetyl-CoA to form malonyl-CoA that plays a key role in the regulation of fatty acid metabolism. The objective of the present study was to investigate the associations of ACCα gene polymorphisms with chicken growth and body composition traits. The Northeast Agricultural University broiler lines divergently selected for abdominal fat content and the Northeast Agricultural University F2 Resource Population were used in the current study. Body weight and body composition traits were measured in the aforementioned two populations. A synonymous mutation was detected in the exon 19 region of ACCα gene, then polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was developed to genotype all the individuals derived from the aforementioned populations. Association analysis revealed that the polymorphism was associated with abdominal fat weight and percentage of abdominal fat in the two populations. The results suggested that ACCα gene could be a candidate locus or linked to a major gene that affects abdominal fat content in the chicken. 相似文献
109.
110.
Adriana R. Rodrigues Henrique Almeida Alexandra M. Gouveia 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(7):1267-1275
The melanocortin system has a clear effect on the mobilisation of stored lipids in adipocytes. The aim of the current study was to investigate the role of melanocortin 5 receptor (MC5R) on α-melanocyte-stimulating hormone (α-MSH)-induced lipolysis in 3T3-L1 adipocytes. To this end, MC5R expression was decreased by small interfering RNA (siRNA), which significantly impaired the α-MSH stimulation of lipolysis, as determined by glycerol and nonesterified fatty-acid (NEFA) quantification. The functional role of α-MSH/MC5R on triglyceride (TG) hydrolysis was mediated by hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), perilipin 1 (PLIN1) and acetyl-CoA carboxylase (ACC). Immunofluorescence microscopy revealed that phosphorylated HSL clearly surrounded lipid droplets in α-MSH-stimulated adipocytes, whereas PLIN1 left the immediate periphery of lipids. These observations were lost when the expression of MC5R was suppressed. 相似文献