全文获取类型
收费全文 | 320篇 |
免费 | 23篇 |
出版年
2022年 | 2篇 |
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 9篇 |
2014年 | 17篇 |
2013年 | 21篇 |
2012年 | 24篇 |
2011年 | 19篇 |
2010年 | 10篇 |
2009年 | 14篇 |
2008年 | 24篇 |
2007年 | 17篇 |
2006年 | 18篇 |
2005年 | 14篇 |
2004年 | 13篇 |
2003年 | 16篇 |
2002年 | 13篇 |
2001年 | 6篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1968年 | 1篇 |
1963年 | 1篇 |
1961年 | 1篇 |
1958年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有343条查询结果,搜索用时 15 毫秒
1.
Alzheimer's disease (AD) is a severe age dependent and chronic problem with no cure so far. The available treatments are temporary, acting over short period of time. The main pathological hallmark of the disease includes cholinergic dysfunction, oxidative stress, accumulation of Aβ fibrils and tau tangles. In context with the multi-factorial nature of this disease, two different series of molecules were developed to hit the multifactorial disease targets. Mainly, the molecules were designed to inhibit the AChE and aggregation of Aβ, and also oxidative damage. Two novel series of TAC-fenbufen/menbutone conjugated molecules were designed, synthesized and bio-assayed. All compounds showed inhibition capacity towards AChE, Aβ aggregation and moderate to good radical scavenging capacity. Particularly, five TAC-menbutone molecules showed improved AChE and Aβ aggregation inhibition capacity compared to TAC-fenbufen conjugated molecules. Overall, these novel series of molecules may be potential drug lead molecules in the treatment of AD. 相似文献
2.
Fossil onagraceous pollen grains from two Upper Miocene localities in E. Austria were investigated by LM and EM. Exine structure and sculpture as well as viscin threads suggest affinities with the extant genusCircea. 相似文献
3.
Using [3H] diazepam as ligand, it is possible to distinguish neuronal binding sites from those present on glial elements and in peripheral tissues (non-neuronal). The function of the "non-neuronal" binding sites is still obscure. Preliminary data showed a distribution of [3H] diazepam binding sites in kidney that could suggest a localization along the renal tubules. This is the site at which a renal peptide, arginine-vasopressin (AVP) is supposed to act. In an attempt to examine the function of these "non-neuronal" sites, we studied the [3H] diazepam binding in kidney of Brattleboro rats which lack AVP and present the symptoms of diabetes insipidus. The homozygous Brattleboro rats showed an increase in the apparent number of benzodiazepine binding sites (Bmax) compared to Long-Evans control rats. Replacement of AVP in these animals results in a reversal of the electrolyte alterations of diabetes insipidus and in an increase of the affinity of the [3H] diazepam binding. These findings may indicate a possible relationship between benzodiazepine binding sites and vasopressin action in kidney and may support receptor function of these "non-neuronal" binding sites. 相似文献
4.
Lisette Waits Stephanie Dunkle F. E. Wilkinson P. Moreau Keri Safranski T. Reust Dorothy M. Morré D. J. Morré 《Protoplasma》1990,154(1):8-15
Summary Transfer of radiolabeled lipids from dictyosome-like structures (DLS) from testis tubules of the guinea pig as donor to unlabeled plasma membrane from testis tubules immobilized on nitrocellulose as acceptor was studied in a completely cell-free system. As a general label for lipids of the donor DLS, isolated testis tubules were incubated with [14C]acetate. Time- and temperature-dependent transfer of [14C]acetate labeled constituents was observed in the cellfree system. However, despite the fact that phospholipids and other constituents were highly labeled in the donor fraction, primarily radioactive sterols were transferred to the plasma membrane acceptor vesicles. Transfer at 37°C represented 0.4 to 0.7% of the total radiolabeled cholesterol at 37°C but little or no transfer occurred at 4°C. The sterols transferred exhibited Chromatographic mobilities corresponding to those of cholesterol and lanosterol. Similar results were obtained with [14C]mevalonic acid. In subsequent experiments, cholesterol transfer from DLS to plasma membrane was demonstrated by incubation of DLS with [3H]squalene which was converted into sterol or with [14C]cholesterol. Transfer of sterols required ATP, but not cytosol, and was both time- and temperature-dependent. DLS were more effective than either endoplasmic reticulum or plasma membrane as the donor fraction. The results from the cell-free analysis suggest a possible functional role of the DLS in sterol biogenesis and transfer to the plasma membrane during spermatid development.Abbreviations DLS
dictyosome-like structure(s)
- PBS
phosphatebuffered saline
- HEPES
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
- BSA
bovine serum albumin 相似文献
5.
Jingru Che Thomas J. DePalma Hemamylammal Sivakumar Louisa S. Mezache Miranda M. Tallman Monica Venere Katelyn Swindle-Reilly Rengasayee Veeraraghavan Aleksander Skardal 《Biotechnology and bioengineering》2023,120(4):1108-1119
Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a three-dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM. 相似文献
6.
7.
G Tallman J E Akers B T Burlingham G R Reeck 《Biochemical and biophysical research communications》1977,79(3):815-822
Histone synthesis decreases approximately in parallel with the decrease in cellular DNA synthesis when KB cell monolayers are productively infected with adenovirus type 2 and does not occur in coordination with the later surge of viral DNA synthesis. The synthesis of histones is not, therefore, required for all replicative DNA synthesis in the nuclei of mammalian cells. 相似文献
8.
Alpha-adrenergic receptors on human platelets. 总被引:4,自引:0,他引:4
[3H] dihydroergocyrptine, an α-adrenergic antagonist, binds specifically to sites on human platelet membranes. Prostaglandin E1 (PGE1) stimulates the production of cyclic AMP (cAMP) in human platelets. Alpha-adrenergic agonists, 1-epinephrine and 1-norepinephrine, and antagonists, phentolamine, phenoxybenzamine, and dihydroergocyrptine inhibit the binding of [3H] dihydroergocryptine. The α-adrenergic agonists inhibit PGE1-stimulated cAMP production and the α-adrenergic antagonists phentolamine and dihydroergocryptine reverse this inhibition. The β-adrenergic agonist 1-isoproterenol and the β-adrenergic antagonists d1-propranolol and 1-alprenolol do not significantly alter binding or PGE1-stimulated cAMP production. Clonidine, dopamine, and serotonin inhibit binding, but clonidine and dopamine are weak inhibitors of PGE1-stimulated cAMP production, and serotonin is without effect. Tyramine, an amine without direct adrenergic activity fails to inhibit binding. Alpha-adrenergic agonists decrease the apparent affinity of a PGE1-receptor activating cAMP production. The inhibition of PGE1-stimulated cAMP production is a physiological measure of α-adrenergic agonist binding to the α-receptor. 相似文献
9.
Radioactive gangliosides, N-[14C]-acetylneuraminylgalactosylglucosylceramide ([14C]GM3) and N- [14C]-acetylneuraminylgalactosyl-N-acetylgalactosaminyl- [N-acetylneuraminyl]-galactosylglucosylceramide ([14C]GD1a), were synthesized from CMP-[14C]sialic acid and the appropriate precursor glycolipid using specific sialyltransferase activities. These compounds were isolated and used as substrates to assay sialidase activity in HeLa cells. Although sodium butyrate added to the culture medium increased GM3 biosynthesis in HeLa cells, sialidase activity, as well as that of other glycohydrolases, was the same in control and butyrate-treated HeLa cells. The same sialidase activity appeared to hydrolyze both [14C]GM3 and [14C]GD1a, but not fetuin; the enzyme had a pH optimum of 5.0 and a Km of 75 μm for the ganglioside substrates. Although the cells contained a high sialidase activity (4–7 nmol/mg of protein/h) and could bind exogenously added [14C]GM3, no “ecto”-sialidase activity would be detected in intact cells under conditions where a close to physiological pH is maintained. The results indicate that ganglioside sialidase is not involved directly in the morphological and biochemical differentiation induced in HeLa cells by exposure to sodium butyrate. 相似文献
10.
Synopsis Pearl dace, Semotilus margarita, are common in slow-moving channels and pools of the headwaters of the Brokenhead River. From May to September age groups 0, 1 and 2+ were partially segregated in space based on water depth with age 0 occupying shallow pools and shallow channels. Age 1 were abundant in shallow pools and deep channels while age 2+ occurred in deep channels and deep pools. In November all age groups coexisted in deep pools. Pearl dace are omnivorous consuming invertebrates, plant material, and detritus. From May to September age groups 0 and 1 consumed mainly terrestrial invertebrates (Diptera, Hymenoptera, Thysanoptera) but age 1 consumed more detritus than age 0. Age 2+ consumed mainly aquatic Diptera larvae. Although all ages consumed aquatic insects almost exclusively in November differences in diet between age groups still existed. Younger fish fed higher in the water column than older fish. Intraspecific resource partitioning of food and space occurs between age groups and this combined with the omnivorous diet is highly adaptive to the headwaters of streams. 相似文献