全文获取类型
收费全文 | 2205篇 |
免费 | 61篇 |
国内免费 | 34篇 |
专业分类
2300篇 |
出版年
2023年 | 10篇 |
2022年 | 25篇 |
2021年 | 38篇 |
2020年 | 43篇 |
2019年 | 24篇 |
2018年 | 35篇 |
2017年 | 23篇 |
2016年 | 28篇 |
2015年 | 52篇 |
2014年 | 126篇 |
2013年 | 132篇 |
2012年 | 84篇 |
2011年 | 161篇 |
2010年 | 114篇 |
2009年 | 89篇 |
2008年 | 119篇 |
2007年 | 117篇 |
2006年 | 86篇 |
2005年 | 73篇 |
2004年 | 88篇 |
2003年 | 60篇 |
2002年 | 46篇 |
2001年 | 23篇 |
2000年 | 30篇 |
1999年 | 27篇 |
1998年 | 29篇 |
1997年 | 29篇 |
1996年 | 30篇 |
1995年 | 28篇 |
1994年 | 29篇 |
1993年 | 35篇 |
1992年 | 32篇 |
1991年 | 27篇 |
1990年 | 28篇 |
1989年 | 23篇 |
1988年 | 29篇 |
1987年 | 19篇 |
1986年 | 24篇 |
1985年 | 29篇 |
1984年 | 44篇 |
1983年 | 44篇 |
1982年 | 43篇 |
1981年 | 39篇 |
1980年 | 31篇 |
1979年 | 20篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 8篇 |
1975年 | 4篇 |
1973年 | 6篇 |
排序方式: 共有2300条查询结果,搜索用时 15 毫秒
91.
We investigated the molecular mechanism of the glucose effect on the regulation of chondrogenesis. Exposure of chick wing bud mesenchymal cells to high concentrations of glucose stimulated chondrogenesis 2–fold to 2.5-fold without affecting cell proliferation. Glucose increased protein levels and the membrane translocation of protein kinase C alpha (PKC), leading to a reduction of extracellular signal-regulated kinase (ERK) phosphorylation. Phosphorylation of p38 was also increased in a PKC-independent manner by glucose treatment. Glucose also increased cell adhesion molecules such as fibronectin, integrin 1, and N-cadherin at early stages and then decreased these adhesion molecules at later stages of chondrogenesis. These alterations in protein level of adhesion molecules and in the phosphorylation of mitogen-activated protein kinases by glucose were blocked by inhibition of PKC or p38 but were synergistically increased by the inhibition of ERK. Therefore, high doses of glucose induce the down-regulation of ERK activity via PKC and the up-regulation of p38 and result in the stimulation of chondrogenesis of chick mesenchymal cells through modulating the expression of adhesion molecules.This work was supported by the Korea Research Foundation (KRF-2000-DP0352) 相似文献
92.
Kunqi Wang Hua Yang Lin Zhu Jianhui Liao Tianhong Lu Wei Xing Shenyang Xing Qiang Lv 《Journal of Molecular Catalysis .B, Enzymatic》2009,58(1-4):194-198
In this paper, it was found that glucose oxidase (GOD) has been stably immobilized on glassy carbon electrode modified by ordered mesoporous silica-SBA-15 and Nafion. The sorption behavior of GOD immobilized on SBA-15 matrix was characterized by transmission electron microscopy (TEM), ultraviolet–visible (UV–vis), FTIR, respectively, which demonstrated that SBA-15 can facilitate the electron exchange between the electroactive center of GOD and electrode. The direct electrochemistry and electrocatalysis behavior of GOD on modified electrode were characterized by cyclic voltammogram (CV) which indicated that GOD immobilized on Nafion and SBA-15 matrices displays direct, nearly reversible and surface-controlled redox reaction with an enhanced electron transfer rate constant of 3.89 s−1 in 0.1 M phosphate buffer solution (PBS) (pH 7.12). Furthermore, it was also discovered that, in the absence of O2, GOD immobilized on Nafion and SBA-15 matrices can produce a wide linear response to glucose in the positive potential range. Thus, Nafion/GOD-SBA-15/GC electrode is hopeful to be used in the third non-mediator's glucose biosensor. In addition, GOD immobilized on SBA-15 and Nafion matrices possesses an excellent bioelectrocatalytic activity for the reduction of O2. The Nafion/GOD-SBA-15/GC electrode can be utilized as the cathode in biofuel cell. 相似文献
93.
Dehydroepiandrosterone decreases elevated hepatic glucose production in C57BL/KsJ-db/db mice 总被引:1,自引:0,他引:1
Aoki K Taniguchi H Ito Y Satoh S Nakamura S Muramatsu K Yamashita R Ito S Mori Y Sekihara H 《Life sciences》2004,74(25):3075-3084
Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia in diabetic db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA suppresses the elevated hepatic gluconeogenic glucose-6-phosphatase (G6Pase) activity and gene expression in C57BL/KsJ-db/db mice. In the present study, we evaluated the total amount of gluconeogenesis using NaH[(14)C]CO(3) and hepatic glucose production using fructose as a substrate in primary cultured hepatocytes. Despite hyperinsulinemia, the glucose production of db/db mice in the total body and hepatocytes was elevated as compared to their heterozygote littermate C57BL/KsJ-db/+m mice. Administration of DHEA significantly decreased the blood glucose level and increased the plasma insulin level in db/db mice. Administration of DHEA decreased the elevated total body and hepatic glucose production in db/db mice. In addition, the glucose production in the primary cultured hepatocytes of db/db mice was decreased significantly by the direct addition of DHEA or DHEA-S to the medium. These results suggest that administration of DHEA suppresses the elevated total body and hepatic glucose production in db/db mice, and this effect on the liver is considered to result from increased plasma insulin and DHEA or DHEA-S itself. 相似文献
94.
Joya E. Nahon Menno Hoekstra Vanessa van Harmelen Patrick C.N. Rensen Ko Willems van Dijk Sander Kooijman Miranda Van Eck 《生物化学与生物物理学报:疾病的分子基础》2019,1865(2):494-501
Objective
Proteoglycan 4 (Prg4) has emerged from human association studies as a possible factor contributing to weight gain, dyslipidemia and insulin resistance. In the current study, we investigated the causal role of Prg4 in controlling lipid and glucose metabolism in mice.Methods
Prg4 knockout (KO) mice and wild-type (WT) littermates were challenged with an obesogenic high-fat diet (45% of total calories as fat) for 16?weeks. To further stimulate the development of metabolic alterations, 10% fructose water was provided starting from week 13.Results
Prg4 deficiency only tended to reduce diet-induced body weight gain, but significantly improved glucose handling (AUC: ?29%; p?<?0.05), which was also reflected by a tendency towards a reduced HOMA-IR score (?49%; p?=?0.06 as compared to WT mice). This coincided with lower hepatic expression of glycolysis (Gck: ?30%; p?<?0.05) and lipogenesis (Acc: ?21%; p?<?0.05 and Scd1: ?38%; p?<?0.001) genes, which translated in significantly lower hepatic triglyceride levels (?56%; p?<?0.001) in Prg4 KO mice as compared to WT mice. Prg4 KO mice likely had lower glucose utilization by skeletal muscle as compared to WT mice, judged by a significant reduction in the genes Glut4 (?29%; p?<?0.01), Pfkm (?21%; p?<?0.05) and Hk2 (?39%; p?<?0.001). Moreover, Prg4 KO mice showed a favorable white adipose tissue phenotype with lower uptake of triglyceride-derived fatty acids (?46%; p?<?0.05) and lower gene expression of inflammatory markers Cd68, Mcp1 and Tnfα (?65%, ?81% and ?63%, respectively; p?<?0.01) than WT mice.Conclusion
Prg4 KO mice are protected from high-fat diet-induced glucose intolerance and fatty liver disease. 相似文献95.
Two new compounds, 5-methyl-2-(2-methylbutanoyl)phloroglucinol 1-O-(6-O-β-D-apiofuranosyl)-β-D-glucopyranoside (1) and trans-2,3-dihydrokaempferol 3-O-(4-O-sulfo)-α-L-arabinopyranoside (2), together with 14 known flavonoids, trans-dihydrokaempferol 3-O-α-L-arabinopyranoside (3), trans-taxifolin 3-O-α-L-arabinofuranoside (4), quercetin 3-O-α-L-rhamnopyranoside (5), quercetin 3'-O-α-L-arabinofuranoside (6), catechin 3-O-α-L-rhamnopyranoside (7), trans-taxifolin 3-O-α-L-arabinopyranoside (8), cis-dihydrokaempferol 3-O-α-L-arabinopyranoside (9), catechin (10), myricetin 3-O-α-L-rhamnopyranoside (11), quercetin 3-O-α-L-arabinopyranoside (12), quercetin 3-O-α-L-arabinofuranoside (13), quercetin 3-O-(3″-galloyl)-α-L-rhamnopyranoside (14), quercetin 3-O-(2″-galloyl)-α-L-rhamnopyranoside (15), and epicatechin 3-O-gallate (16), were isolated from the leaves of Ruprechtia polystachya Griseb. (Polygonaceae). Their structures were established on the basis of extensive 1D- and 2D-NMR experiments as well as MS analyses. All compounds, except 1, showed inhibition of the enzyme glucose-6-phosphatase in intact microsomes. 相似文献
96.
将酶电极应用于发酵糖的测定时。与糖共存的乙醇常常会影响测糖的准确性,通过对葡萄糖氧化酶(GOD)电极的研究,探讨了乙醇对测糖酶电极测定影响,进而研制出抗干扰的GOD酶电极,若是GOD电极的酶膜通过夹心法制备.在乙醇含量为0.1%(V/V)时·即产生显著的影响,使测定结果偏大4.3%,且乙醇的影响随浓度的升高而增大,若用尼龙网固定GOD膜,GOD电极在测定20mmol/L和5mm01/L左右的葡萄糖溶液时,含量高达9%的乙醇仍未对测定产生显著的影响.表现出良好的不受乙醇干扰的特性,并且,该尼龙网GOD电极具有良好的重复性、稳定的响应活性及较长的保存期. 相似文献
97.
Defective Glucose Transport Across Brain Tissue Barriers: A Newly Recognized Neurological Syndrome 总被引:6,自引:0,他引:6
Klepper J Wang D Fischbarg J Vera JC Jarjour IT O'Driscoll KR De Vivo DC 《Neurochemical research》1999,24(4):587-594
Impaired glucose transport across brain tissue barriers causes infantile seizures, developmental delay and acquired microcephaly. Since the first report in 1991 (De Vivo et al, NEJM, 1991) 17 patients have been identified with the glucose transporter protein syndrome (GTPS). The diagnostic feature of the syndrome is an unexplained hypoglycorrhachia in the clinical setting of an infantile epileptic encephalopathy. We review our clinical experience by highlighting one illustrative case: a 6-year old girl who presented at age 2 months with infantile seizures and hypoglycorrhachia. The CSF/blood glucose ratio was 0.33. DNA sequencing identified a missense mutation in exon 7 (C1108T). Erythrocyte GLUT1 immunoreactivity was normal. The time course of 3-0-methyl-glucose (3OMG) uptake by erythrocytes of the patient was 46% that of mother and father. The apparent Km was similar in all cases (2–4 mmol/L), but the apparent Vmax in the patient was only 28% that of the parents (500 versus 1,766 fmol/s/106RBC; p < 0.004). In addition, a 3-month trial of oral thioctic acid also benefited the patient and increased the Vmax to 935 fmol/s/106 RBC (p < 3 × 10–7). Uptake of dehydroascorbic acid by erythrocytes of the patient was impaired to the same degree as that of 3OMG (Vmax was 38% of that of the mother's), which supports previous observations of GLUT1 being multifunctional. These studies confirm the molecular basis of the GTPS and the multifunctional role of GLUT1. The need for more effective treatment is compelling. 相似文献
98.
Davis KB 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2004,139(4):433-440
Sunshine bass (Morone chrysopsxMorone saxatilis) were subjected to a 15-min low-water confinement stressor at temperatures ranging from 5 to 30 degrees C. Physiological responses were evaluated by measuring hematocrit, and plasma chloride, glucose and cortisol. Fish acclimated to 30 degrees C had initial glucose concentrations of 3.13 mM (564 mg/L) which were significantly lower than in fish acclimated to 5 and 10 degrees C (4.32 and 4.82 mM or 779 and 868 mg/l, respectively). Fish survived the conditions imposed at every temperature except 30 degrees C, where 15 out of 42 fish died during the stress and recovery protocol. The general pattern was an initial increase in hematocrit, followed by a delayed decrease in hematocrit and chloride, and an increase in plasma glucose and cortisol. In general, fish stressed at temperatures below 20 degrees C had lower and more delayed changes in plasma glucose and cortisol than fish tested at 20, 25 and 30 degrees C. Initial cortisol concentrations were 65 ng/ml and increased to above 200 ng/ml in fish held at 20 degrees C and above. At the higher temperatures, glucose concentrations were twice the initial concentration after stress and cortisol changes were four to five times the initial concentration after the stress. Quantitative responses for glucose and cortisol were moderate and recovery rapid in fish stressed at 10 and 15 degrees C; therefore, this range of water temperature is recommended when handling sunshine bass. 相似文献
99.
In this study we report the cloning and characterisation of the mouse Glut12 gene and examine for the first time its expression pattern in the earliest stages of development. Mouse Glut12 (mGlut12) was cloned from preimplantation embryos by 5'RACE RT-PCR using primers designed from an EST clone corresponding to a human GLUT12 antigenic sequence after positive immunoreactivity was observed in mouse two-cell embryos by western immunoblotting. The mGlut12 gene contains an open reading frame of 1869 base pairs, potentially encoding a polypeptide of 622 amino acids. The predicted mGLUT12 protein bears all the hallmarks of the SLC2A family of hexose transporters and shares an 83% sequence homology to human GLUT12. Consistent with its human homolog mGlut12 mRNA is found highly expressed in skeletal and cardiac muscle and fat. Additionally, it was also found in the uterus and during early embryogenesis. During early development in the mouse, Glut12 expression is clearly apparent in ovulated oocytes and two-cell embryos but declines in day 3 morulae. With the exception of some Glut12 expression apparent in blastocysts, Glut12 mRNA remains at low to undetectable levels until E11. 相似文献
100.
We have previously demonstrated that ET-1 may enhance glucose transport in 3T3-L1 adipocytes, secondarily to its stimulatory effect on GLUT1 gene expression by a mitogen-activated protein kinase (MAPK)-dependent pathway. In the present study, we further tested the involvement of Ca2+ in glucose uptake in response to ET-1. Among a variety of Ca2+-related agents tested, EGTA and thapsigargin were found to suppress both the glucose uptake and intracellular Ca2+ mobilization induced by ET-1, as determined by Fura-2 analysis. However, a phospholipase C inhibitor, U73122, also eliminated the intracellular calcium mobilization induced by ET-1, but had no effect on ET-1-stimulated glucose uptake. The finding that neither EGTA nor thapsigargin had any influence on ET-1-induced MAPK activation implies that some mechanism downstream of MAPK activation is involved. Further investigation showed that both agents exerted global inhibitory effects on protein and RNA syntheses. Since both thapsigargin and EGTA may deplete endoplasmic reticulum (ER) Ca2+ stores, our results suggest that (1) ET-1-induced glucose transport is independent of ET-1's effect on Ca2+ mobilization and (2) depletion of ER Ca2+ stores per se may interfere with ET-1's effect on GLUT1 expression. 相似文献