全文获取类型
收费全文 | 1111篇 |
免费 | 70篇 |
国内免费 | 2篇 |
专业分类
1183篇 |
出版年
2022年 | 9篇 |
2021年 | 11篇 |
2018年 | 16篇 |
2017年 | 7篇 |
2016年 | 21篇 |
2015年 | 18篇 |
2014年 | 20篇 |
2013年 | 43篇 |
2012年 | 46篇 |
2011年 | 47篇 |
2010年 | 30篇 |
2009年 | 30篇 |
2008年 | 50篇 |
2007年 | 48篇 |
2006年 | 52篇 |
2005年 | 43篇 |
2004年 | 42篇 |
2003年 | 40篇 |
2002年 | 31篇 |
2001年 | 42篇 |
2000年 | 34篇 |
1999年 | 30篇 |
1998年 | 19篇 |
1997年 | 7篇 |
1996年 | 11篇 |
1995年 | 11篇 |
1994年 | 16篇 |
1993年 | 9篇 |
1992年 | 20篇 |
1991年 | 19篇 |
1990年 | 14篇 |
1989年 | 24篇 |
1988年 | 27篇 |
1987年 | 14篇 |
1986年 | 32篇 |
1985年 | 21篇 |
1984年 | 21篇 |
1983年 | 16篇 |
1982年 | 11篇 |
1981年 | 8篇 |
1980年 | 10篇 |
1979年 | 25篇 |
1978年 | 18篇 |
1977年 | 9篇 |
1976年 | 12篇 |
1975年 | 21篇 |
1974年 | 15篇 |
1973年 | 11篇 |
1972年 | 7篇 |
1971年 | 6篇 |
排序方式: 共有1183条查询结果,搜索用时 0 毫秒
81.
AMPK beta subunit targets metabolic stress sensing to glycogen 总被引:12,自引:0,他引:12
Polekhina G Gupta A Michell BJ van Denderen B Murthy S Feil SC Jennings IG Campbell DJ Witters LA Parker MW Kemp BE Stapleton D 《Current biology : CB》2003,13(10):867-871
AMP-activated protein kinase (AMPK) is a multisubstrate enzyme activated by increases in AMP during metabolic stress caused by exercise, hypoxia, lack of cell nutrients, as well as hormones, including adiponectin and leptin. Furthermore, metformin and rosiglitazone, frontline drugs used for the treatment of type II diabetes, activate AMPK. Mammalian AMPK is an alphabetagamma heterotrimer with multiple isoforms of each subunit comprising alpha1, alpha2, beta1, beta2, gamma1, gamma2, and gamma3, which have varying tissue and subcellular expression. Mutations in the AMPK gamma subunit cause glycogen storage disease in humans, but the molecular relationship between glycogen and the AMPK/Snf1p kinase subfamily has not been apparent. We show that the AMPK beta subunit contains a functional glycogen binding domain (beta-GBD) that is most closely related to isoamylase domains found in glycogen and starch branching enzymes. Mutation of key glycogen binding residues, predicted by molecular modeling, completely abolished beta-GBD binding to glycogen. AMPK binds to glycogen but retains full activity. Overexpressed AMPK beta1 localized to specific mammalian subcellular structures that corresponded with the expression pattern of glycogen phosphorylase. Glycogen binding provides an architectural link between AMPK and a major cellular energy store and juxtaposes AMPK to glycogen bound phosphatases. 相似文献
82.
Simanshu DK Satheshkumar PS Savithri HS Murthy MR 《Biochemical and biophysical research communications》2003,311(1):193-201
Propionate metabolism in Salmonella typhimurium occurs via 2-methylcitric acid cycle. The last step of this cycle, the cleavage of 2-methylisocitrate to succinate and pyruvate, is catalysed by 2-methylisocitrate lyase (PrpB). Here we report the X-ray crystal structure of the native and the pyruvate/Mg(2+) bound PrpB from S. typhimurium, determined at 2.1 and 2.3A, respectively. The structure closely resembles that of the Escherichia coli enzyme. Unlike the E. coli PrpB, Mg(2+) could not be located in the native Salmonella PrpB. Only in pyruvate bound PrpB structure, Mg(2+) was found coordinated with pyruvate. Binding of pyruvate to PrpB seems to induce movement of the Mg(2+) by 2.5A from its position found in E. coli native PrpB. In both the native enzyme and pyruvate/Mg(2+) bound forms, the active site loop is completely disordered. Examination of the pocket in which pyruvate and glyoxalate bind to 2-methylisocitrate lyase and isocitrate lyase, respectively, reveals plausible rationale for different substrate specificities of these two enzymes. Structural similarities in substrate and metal atom binding site as well as presence of similar residues in the active site suggest possible similarities in the reaction mechanism. 相似文献
83.
84.
Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation 总被引:27,自引:0,他引:27
Garcia Soriano F Virág L Jagtap P Szabó E Mabley JG Liaudet L Marton A Hoyt DG Murthy KG Salzman AL Southan GJ Szabó C 《Nature medicine》2001,7(1):108-113
Diabetic patients frequently suffer from retinopathy, nephropathy, neuropathy and accelerated atherosclerosis. The loss of endothelial function precedes these vascular alterations. Here we report that activation of poly(ADP-ribose) polymerase (PARP) is an important factor in the pathogenesis of endothelial dysfunction in diabetes. Destruction of islet cells with streptozotocin in mice induced hyperglycemia, intravascular oxidant production, DNA strand breakage, PARP activation and a selective loss of endothelium-dependent vasodilation. Treatment with a novel potent PARP inhibitor, starting after the time of islet destruction, maintained normal vascular responsiveness, despite the persistence of severe hyperglycemia. Endothelial cells incubated in high glucose exhibited production of reactive nitrogen and oxygen species, consequent single-strand DNA breakage, PARP activation and associated metabolic and functional impairment. Basal and high-glucose-induced nuclear factor-kappaB activation were suppressed in the PARP-deficient cells. Our results indicate that PARP may be a novel drug target for the therapy of diabetic endothelial dysfunction. 相似文献
85.
Aravinthan DT Samuel Venkatesh N Murthy Michael O Hengartner 《BMC developmental biology》2001,1(1):8-6
Background
Of the animals typically used to study fertilization-induced calcium dynamics, none is as accessible to genetics and molecular biology as the model organism Caenorhabditis elegans. Motivated by the experimental possibilities inherent in using such a well-established model organism, we have characterized fertilization-induced calcium dynamics in C. elegans.Results
Owing to the transparency of the nematode, we have been able to study the calcium signal in C. elegans fertilization in vivo by monitoring the fluorescence of calcium indicator dyes that we introduce into the cytosol of oocytes. In C. elegans, fertilization induces a single calcium transient that is initiated soon after oocyte entry into the spermatheca, the compartment that contains sperm. Therefore, it is likely that the calcium transient is initiated by contact with sperm. This calcium elevation spreads throughout the oocyte, and decays monotonically after which the cytosolic calcium concentration returns to that preceding fertilization. Only this single calcium transient is observed.Conclusion
Development of a technique to study fertilization induced calcium transients opens several experimental possibilities, e.g., identification of the signaling events intervening sperm binding and calcium elevation, identifying the possible roles of the calcium elevation such as the completion of meiosis, the formation of the eggshell, and the establishing of the embryo's axis of symmetry. 相似文献86.
Bioremediation of DDT in soil by genetically improved strains of soil fungus Fusarium solani 总被引:1,自引:0,他引:1
Bioremediation of DDT in soil by genetically improved recombinants of the soil fungus Fusarium solani was studied. The parent strains were isolated from soil enriched with DDD or DDE (immediate anaerobic and aerobic degradation products of DDT), as further degradation of these products are slow processes compared to the parent compound. These naturally occurring strains isolated from soil, however, are poor degraders of DDT and differed in their capability to degrade its metabolites such as DDD, DDE, DDOH and DBP and other organochlorine pesticides viz. kelthane and lindane. Synergistic effect was shown by some of these strains, when grown together in the medium containing DDD and kelthane under mixed culture condition. No synergism in DDE degradation was observed with the strains isolated from enriched soil. DDD-induced proteins extracted from individual culture filtrate (exo-enzyme) when subjected to SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) showed complementary polypeptide bands in these strains i.e., each strain produced distinct DDD degrading polypeptide bands and the recombinant or hybrid strains produced all of the bands of the two parents and degraded DDD better than the parental strains. Recombinant hybrid strains with improved dehalogenase activity were raised by parasexual hybridisation of two such complementary isolates viz. isolate 1(P-1) and 4(P-2) showing highest complementation and are compatible for hyphal fusion inducing heterokaryosis. These strains are genetically characterised as Kel+BenRDBP-Lin- and Kel-BenrDBP+Lin+ respectively.Recombinants with mixed genotype, i.e., Kel+BenRDBP+Lin+ showing superior degradation quality for DDT were selected for bioremediation study. Recombination was confirmed by polypeptide band analysis of DDD induced exo-proteins from culture filtrate usingSDS-Polyacrylamide Gel Electrophoresis (PAGE) and RAPD (Random Amplified Polymorphic DNA) of genomic DNA using PCR (Polymerase Chain Reaction) technique. SDS-PAGE showed combination of DDD induced polypeptide bands characteristic of both the parents in the recombinants or the hybrids. PCR study showed the parent specific bands in the recombinant strains confirming gene transformation. 相似文献
87.
Murthy M Hamilton J Greiner RS Moriguchi T Salem N Kim HY 《Journal of lipid research》2002,43(4):611-617
In this study, we have examined the effects of n-3 fatty acid deficient diets on the phospholipids (PL) molecular species composition in the hippocampus. Female rats were raised for two generations on diets containing linoleic acid (18:2n-6), with or without supplementation of alpha-linolenic acid (18:3n-3) or 18:3n-3 plus docosahexaenoic acid (22:6n-3). At 84 days of age, the hippocampal phospholipids were analyzed by reversed phase HPLC-electrospray ionization mass spectrometry. Depleting n-3 fatty acids from the diet led to a reduction of 22:6n-3 molecular species in phosphatidylcholine (PC), phosphatidylethanolamine (PE), PE-plasmalogens (PLE), and phosphatidylserine (PS) by 70-80%. In general, 22:6n-3 was replaced with 22:5n-6 but the replacement at the molecular species level did not always occur in a reciprocal manner, especially in PC and PLE. In PC, the 16:0,22:6n-3 species was replaced by 16:0,22:5n-6 and 18:0,22:5n-6. In PLE, substantial increases of both 22:5n-6 and 22:4n-6 species compensated for the decreases in 22:6n-3 species in n-3 fatty acid deficient groups. While the total PL content was not affected by n-3 deficiency, the relative distribution of PS decreased by 28% with a concomitant increase in PC.The observed decrease of 22:6n-3 species along with PS reduction may represent key biochemical changes underlying losses in brain-hippocampal function associated with n-3 deficiency. 相似文献
88.
Fritillaria thunbergii Miq. bulb-scale sections were cultured using Murashige and Skoog (MS) medium supplemented with NAA (1.62 M) and KN/2iP/BA (0.47–23.23 M).A high frequency of bulblets was developed from the scale sections and these bulblets have developed leaves and roots in 12 weeks of culture. An optimum of 13.7 bulblets developed from scale sections on solid MS medium supplemented with 1.62 M NAA and 4.65 M KN. Cultures incubated under cycles of 16 h white fluorescent light (40 mol m–2 s–1) and 8 h dark at a temperature regime of 25°C have produced optimal bulblets compared to cultures incubated under continuous dark at 25°C. The bulblets were harvested at the end of culture period and were given cold treatment at 5°C for 5 weeks and then transplanted to a potting mixture of peat moss, vermiculite and perlite (1:1:1). The bulblets, which were more than 10 mm in diameter, sprouted (100%) in 5 weeks of transplantation. 相似文献
89.
90.
Phytochemical investigation of the roots and aerial parts of Andrographis paniculata Nees yielded a new flavone, 5-hydroxy-7,2',6'-trimethoxyflavone and an unusual 23-carbon terpenoid, 14-deoxy-15-isopropylidene-11,12-didehydroandrographolide together with five known flavonoids and four known diterpenoids. The structures of these compounds were determined on the basis of spectral and chemical studies. 相似文献