全文获取类型
收费全文 | 526篇 |
免费 | 30篇 |
专业分类
556篇 |
出版年
2023年 | 5篇 |
2022年 | 8篇 |
2021年 | 13篇 |
2020年 | 8篇 |
2019年 | 9篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 17篇 |
2015年 | 26篇 |
2014年 | 30篇 |
2013年 | 34篇 |
2012年 | 43篇 |
2011年 | 44篇 |
2010年 | 25篇 |
2009年 | 20篇 |
2008年 | 23篇 |
2007年 | 26篇 |
2006年 | 30篇 |
2005年 | 26篇 |
2004年 | 25篇 |
2003年 | 26篇 |
2002年 | 16篇 |
2001年 | 3篇 |
2000年 | 5篇 |
1999年 | 9篇 |
1998年 | 6篇 |
1997年 | 9篇 |
1996年 | 10篇 |
1995年 | 10篇 |
1994年 | 2篇 |
1993年 | 7篇 |
1992年 | 6篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1971年 | 2篇 |
1957年 | 1篇 |
排序方式: 共有556条查询结果,搜索用时 15 毫秒
71.
72.
73.
Bianca T. A. de Greef Janneke G. J. Hoeijmakers Emma E. Wolters Hubertus J. M. Smeets Arthur van den Wijngaard Ingemar S. J. Merkies Catharina G. Faber Monique M. Gerrits 《PloS one》2016,11(2)
Objective
Screening for Fabry disease in patients with small fiber neuropathy has been suggested, especially since Fabry disease is potentially treatable. However, the diagnostic yield of testing for Fabry disease in isolated small fiber neuropathy patients has never been systematically investigated. Our aim is to determine the presence of Fabry disease in patients with small fiber neuropathy.Methods
Patients referred to our institute, who met the criteria for isolated small fiber neuropathy were tested for Fabry disease by measurement of alpha-Galactosidase A activity in blood, lysosomal globotriaosylsphingosine in urine and analysis on possible GLA gene mutations.Results
725 patients diagnosed with small fiber neuropathy were screened for Fabry disease. No skin abnormalities were seen except for redness of the hands or feet in 30.9% of the patients. Alfa-Galactosidase A activity was tested in all 725 patients and showed diminished activity in eight patients. Lysosomal globotriaosylsphingosine was examined in 509 patients and was normal in all tested individuals. Screening of GLA for mutations was performed for 440 patients, including those with diminished α-Galactosidase A activity. Thirteen patients showed a GLA gene variant. One likely pathogenic variant was found in a female patient. The diagnosis Fabry disease could not be confirmed over time in this patient. Eventually none of the patients were diagnosed with Fabry disease.Conclusions
In patients with isolated small fiber neuropathy, and no other signs compatible with Fabry disease, the diagnostic yield of testing for Fabry disease is extremely low. Testing for Fabry disease should be considered only in cases with additional characteristics, such as childhood onset, cardiovascular disease, renal failure, or typical skin lesions. 相似文献74.
Delacour D Cramm-Behrens CI Drobecq H Le Bivic A Naim HY Jacob R 《Current biology : CB》2006,16(4):408-414
The central aspect of epithelial cells is their polarized structure, characterized by two distinct domains of the plasma membrane, the apical and the basolateral membrane. Apical protein sorting requires various signals and different intracellular routes to the cell surface. The first apical targeting motif identified is the membrane anchoring of a polypeptide by glycosyl-phosphatidyl-inositol (GPI). A second group of apical signals involves N- and O-glycans, which are exposed to the luminal side of the sorting organelle. Sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH), which use separate transport platforms for trafficking, are two model proteins for the study of apical protein sorting. In contrast to LPH, SI associates with sphingolipid/cholesterol-enriched membrane microdomains or "lipid rafts". After exit form the trans-Golgi network (TGN), the two proteins travel in distinct vesicle populations, SAVs (SI-associated vesicles) and LAVs (LPH-associated vesicles) . Here, we report the identification of the lectin galectin-3 delivering non-raft-dependent glycoproteins in the lumen of LAVs in a carbohydrate-dependent manner. Depletion of galectin-3 from MDCK cells results in missorting of non-raft-dependent apical membrane proteins to the basolateral cell pole. This suggests a direct role of galectin-3 in apical sorting as a sorting receptor. 相似文献
75.
76.
The aims of this study were to characterize the hysterographic and histological features of the uteri and to perform immunohistochemistry with proliferating cell nuclear antigen (PCNA) in the cat endometrium at various stages of the reproductive cycle and after treatment with exogenous progestagen. Seventy-four female domestic cats submitted for routine ovariohysterectomy were categorized into six groups: inactive (n=20), follicular (n=9), luteal (n=18), and postpartum (n=12) stages of the reproductive cycle; cats given medroxyprogesterone acetate for estrus prevention (MPA group) (n=12); and cats with uterine pathological lesions (n=3). Hysterography was performed and the relation of the uterine and luminal shape in the hysterogram with the stage of the reproductive cycle as well as with any pathological conditions of the uterus was evaluated. The uteri and ovaries were thereafter surgically removed and sectioned for histological examination. The PCNA was used to demonstrate the expression of endometrial epithelial cell growth. The hysterographic appearance was found to differ between the six groups of cats. A straight uterine cavity was characteristic for cats in the inactive stage, whereas a wavy uterine cavity was characteristic for cats in the follicular stage. In the luteal stage, the luminal cavity of the uteri differed in shape with increasing progesterone concentration from straight to irregular wavy or coiled. The coil shaped uterine lumen seen in the MPA treated and pathological groups was considered also to be an expression of a progestagenic effect. Waviness and coiling of the uterine lumen was related to a proliferation of the endometrial glands, whereas irregular filling defects were indicative of endometrial cystic changes. This study is the first to demonstrate the expression of PCNA in the cat endometrium although no differences were found between the six groups of cats. The hysterographic appearance was found to differ according to stage of the reproductive cycle and pathological conditions. Thus, a normative hysterogram is now available for diagnosing the reproductive stage and uterine changes in cats developing endometrial hyperplasia with and without cystic changes. 相似文献
77.
Nantapong N Otofuji A Migita CT Adachi O Toyama H Matsushita K 《Bioscience, biotechnology, and biochemistry》2005,69(1):149-159
Type II NADH dehydrogenase of Corynebacterium glutamicum (NDH-2) was purified from an ndh overexpressing strain. Purification conferred 6-fold higher specific activity of NADH:ubiquinone-1 oxidoreductase with a 3.5-fold higher recovery than that previously reported (K. Matsushita et al., 2000). UV-visible and fluorescence analyses of the purified enzyme showed that NDH-2 of C. glutamicum contained non-covalently bound FAD but not covalently bound FMN. This enzyme had an ability to catalyze electron transfer from NADH and NADPH to oxygen as well as various artificial quinone analogs at neutral and acidic pHs respectively. The reduction of native quinone of C. glutamicum, menaquinone-2, with this enzyme was observed only with NADH, whereas electron transfer to oxygen was observed more intensively with NADPH. This study provides evidence that C. glutamicum NDH-2 is a source of the reactive oxygen species, superoxide and hydrogen peroxide, concomitant with NADH and NADPH oxidation, but especially with NADPH oxidation. Together with this unique character of NADPH oxidation, phylogenetic analysis of NDH-2 from various organisms suggests that NDH-2 of C. glutamicum is more closely related to yeast or fungal enzymes than to other prokaryotic enzymes. 相似文献
78.
Two isoforms of a heme oxygenase gene, ho1 and ho2, with 51% identity in amino acid sequence have been identified in the cyanobacterium Synechocystis sp. PCC 6803. Isoform-1, Syn HO-1, has been characterized, while isoform-2, Syn HO-2, has not. In this study, a full-length ho2 gene was cloned using synthetic DNA and Syn HO-2 was demonstrated to be highly expressed in Escherichia coli as a soluble, catalytically active protein. Like Syn HO-1, the purified Syn HO-2 bound hemin stoichiometrically to form a heme-enzyme complex and degraded heme to biliverdin IXalpha, CO and iron in the presence of reducing systems such as NADPH/ferredoxin reductase/ferredoxin and sodium ascorbate. The activity of Syn HO-2 was found to be comparable to that of Syn HO-1 by measuring the amount of bilirubin formed. In the reaction with hydrogen peroxide, Syn HO-2 converted heme to verdoheme. This shows that during the conversion of hemin to alpha-meso-hydroxyhemin, hydroperoxo species is the activated oxygen species as in other heme oxygenase reactions. The absorption spectrum of the hemin-Syn HO-2 complex at neutral pH showed a Soret band at 412 nm and two peaks at 540 nm and 575 nm, features observed in the hemin-Syn HO-1 complex at alkaline pH, suggesting that the major species of iron(III) heme iron at neutral pH is a hexa-coordinate low spin species. Electron paramagnetic resonance (EPR) revealed that the iron(III) complex was in dynamic equilibrium between low spin and high spin states, which might be caused by the hydrogen bonding interaction between the distal water ligand and distal helix components. These observations suggest that the structure of the heme pocket of the Syn HO-2 is different from that of Syn HO-1. 相似文献
79.
Danielsen S Strand S de Lange Davies C Stokke BT 《Biochimica et biophysica acta》2005,1721(1-3):44-54
Chitosan-based gene delivery systems are promising candidates for non-viral gene therapy. A wide range of chitosans has been studied to optimize the properties of the DNA-chitosan complexes to yield high transfection efficiencies. An important parameter to control is the polyplex stability to allow transport towards the cells, subsequent internalization and release of DNA intracellularly. The stability of the DNA-chitosan complexes was here studied after exposure to heparin and hyaluronic acid (HA) using atomic force microscopy (AFM) and ethidium bromide (EtBr) fluorescence assay. To study the effect of polycation chain length on the polyplex stability, chitosans with a degree of polymerization (DP) varying from approximately 10 to approximately 1000 were employed for DNA compaction. Whereas HA was unable to dissociate the complexes, the degree of dissociation caused by heparin depended on both the chitosan chain length and the amount of chitosan used for complexation. When increasing the chitosan concentration, larger heparin concentrations were required for polyplex dissociation. Furthermore, increasing the chitosan chain length yielded more stable complexes. Varying the chitosan chain length thus provides a tool for controlling the ability of the polyplex to deliver therapeutic gene vectors to cells. 相似文献
80.
The human endocrinological disorder polycystic ovary syndrome (PCOS) is a common cause of reproductive failure. Even though the cause of PCOS is unknown, hormone and immune disturbances as well as hyperactivity in the sympathetic nervous system are likely to be involved in the pathogenesis of the disease. The present study was undertaken to elucidate if rats with estradiol valerate (EV)-induced polycystic ovaries (PCO) have altered beta-endorphin concentrations in the hypothalamus and in plasma and if they have alterations in circulating immune cell populations and the activity. Repeated low-frequency (2 Hz) electroacupuncture (EA) treatments are known to modulate the release of beta-endorphin, immune responses, and the activity in the autonomic nervous system. We therefore also investigated the effect of EA treatments on the beta-endorphin and the immune systems. Low-frequency EA was given 12 times, 25 min each, over 30 days starting 2-3 days after i.m. injection of EV. The beta-endorphin concentrations in the hypothalamus and in plasma as well as the frequencies of CD4+ T cells and CD8+ T cells were significantly lower in EV-injected control rats as compared to oil-injected control rats. Repeated EA treatments in EV-injected rats significantly increased beta-endorphin concentrations in the hypothalamus. In conclusion, these findings show that both the beta-endorphinergic and the immune system are significantly impaired in rats with steroid-induced PCO and that repeated EA treatments can restore some of these disturbances. 相似文献