全文获取类型
收费全文 | 396篇 |
免费 | 19篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 13篇 |
2019年 | 10篇 |
2018年 | 13篇 |
2017年 | 13篇 |
2016年 | 25篇 |
2015年 | 16篇 |
2014年 | 35篇 |
2013年 | 31篇 |
2012年 | 27篇 |
2011年 | 32篇 |
2010年 | 20篇 |
2009年 | 13篇 |
2008年 | 23篇 |
2007年 | 16篇 |
2006年 | 17篇 |
2005年 | 19篇 |
2004年 | 17篇 |
2003年 | 13篇 |
2002年 | 6篇 |
2001年 | 7篇 |
2000年 | 11篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
排序方式: 共有415条查询结果,搜索用时 171 毫秒
101.
Mustafa Numan Bucak Pürhan Barbaros Tuncer Serpil Sarıözkan Nuri Başpınar Mehmet Taşpınar Kenan Çoyan Ali Bilgili Pınar Peker Akalın Serhat Büyükleblebici Sena Aydos Seda Ilgaz Asuman Sunguroğlu Derya Öztuna 《Cryobiology》2010,61(3):248-253
This study was conducted to determine the effects of methionine, inositol and carnitine on sperm (motility, abnormality, DNA integrity and in vivo fertility) and oxidative stress parameters (lipid peroxidation, total glutathione and antioxidant potential levels) of bovine semen after the freeze–thawing process. Nine ejaculates, collected with the aid of an artificial vagina twice a week from each Simmental bovine, were included in the study. Each ejaculate, splitted into seven equal groups and diluted in Tris-based extender containing methionine (2.5 and 7.5 mM), carnitine (2.5 and 7.5 mM), inositol (2.5 and 7.5 mM) and no additive (control), was cooled to 5 °C and then frozen in 0.25 ml straws. Frozen straws were then thawed individually at 37 °C for 20 s in a water bath for the evaluation.The extender supplemented with 7.5 mM doses of carnitine and inositol led to higher subjective motility percentages (61.9 ± 1.3% and 51.3 ± 1.6%) compared to the other groups. The addition of methionine and carnitine at doses of 2.5 and 7.5 mM and inositol at doses of 7.5 mM provided a greater protective effect in the percentages of total abnormality in comparison to the control and inositol 2.5 mM (P < 0.001). As regards CASA motility, 7.5 mM carnitine (41.6 ± 2.9% and 54.2 ± 4.9%) and inositol (34.9 ± 2.0% and 47.3 ± 2.2%) caused insignificant increases in CASA and total motility in comparison to the other groups. All of the antioxidants at 2.5 and 7.5 mM resulted in lower sperm with damaged DNA than that of control, thus reducing the DNA damage (P < 0.05). No significant differences were observed in CASA progressive motility and sperm motion characteristics among the groups. In fertility results based on 59-day non-returns, no significant differences were observed in non-return rates among groups. As regards biochemical parameters, supplementation with antioxidants did not significantly affect LPO and total GSH levels in comparison to the control group (P > 0.05). The maintenance of AOP level in methionine 2.5 mM was demonstrated to be higher (5.06 ± 0.38 mM) than that of control (0.96 ± 0.29 mM) following the freeze–thawing (P < 0.001). Supplementation with these antioxidants prior to the cryopreservation process protected the DNA integrity against the cryodamage. Furthermore, future research should focus on the molecular mechanisms of the antioxidative effects of the antioxidants methionine, carnitine and inositol during cryopreservation. 相似文献
102.
Multiplexing RMCE: Versatile Extensions of the Flp-Recombinase-Mediated Cassette-Exchange Technology
Soeren Turan 《Journal of molecular biology》2010,402(1):52-69
There are strong indications, but as yet no proof, that extended 48-bp Flp recombinase targets (FRTs) represent unique targets in all eukaryotic genomes investigated, and that recombinase-mediated cassette exchange is not hampered by the occurrence of genomic pseudo sites. This encouraged the present study in which we explore the feasibility of exchanging, in a given cell, two distinct genomically anchored cassettes, each flanked by a unique set of two heterospecific FRT sites. Mutant FRTs have to meet two major prerequisites for successful recombinase-mediated cassette exchange: (i) a self-recognition capacity comparable to a pair of FRT wild-type sites (FRT × FRT ), and (ii) a negligible cross-interaction if part of a set of heterospecific sites (F′ × F). We apply a two-step strategy to explore various newly created FRT spacer mutants for these properties. As a result of our screening steps, we identify combinations of sites that are successfully applied to parallel Flp-mediated genomic targeting (“multiplexing”) reactions (i.e., the simultaneous exchange of two separate target cassettes in a given cell). 相似文献
103.
Won J Kim M Kim N Ahn JH Lee WG Kim SS Chang KY Yi YW Kim TK 《Nature chemical biology》2006,2(7):369-374
Most somatic cells encounter an inevitable destiny, senescence. Little progress has been made in identifying small molecules that extend the finite lifespan of normal human cells. Here we show that the intrinsic 'senescence clock' can be reset in a reversible manner by selective modulation of the ataxia telangiectasia-mutated (ATM) protein and ATM- and Rad3-related (ATR) protein with a small molecule, CGK733. This compound was identified by a high-throughput phenotypic screen with automated imaging. Employing a magnetic nanoprobe technology, magnetism-based interaction capture (MAGIC), we identified ATM as the molecular target of CGK733 from a genome-wide screen. CGK733 inhibits ATM and ATR kinase activities and blocks their checkpoint signaling pathways with great selectivity. Consistently, siRNA-mediated knockdown of ATM and ATR induced the proliferation of senescent cells, although with lesser efficiency than CGK733. These results might reflect the specific targeting of the kinase activities of ATM and ATR by CGK733 without affecting any other domains required for cell proliferation. 相似文献
104.
Polyphenol oxidase (PPO) of Thymbra (Thymbra spicata L. var. spicata) was isolated by (NH4)2SO4 precipitation and dialysis. A diphenolase from Thymbra plant, active against 4-methylcatechol, catechol and pyrogallol was characterized in detail in terms of pH and temperature optima, stability, kinetic parameters and inhibition behaviour towards some general PPO inhibitors. 4-Methylcatechol was the most suitable substrate, due to the lowest Km and the biggest Vmax/Km values, followed by catechol and pyrogallol. The Thymbra PPO had maximum activity at pH 5.0, 7.0 and 8.0 with 4-methylcatechol, catechol and pyrogallol substrates, respectively. The optimum temperature of activity for Thymbra PPO was 30, 40 and 50 °C for 4-methylcatechol, catechol and pyrogallol substrates, respectively. It was found that optimum temperature and pH were substrate-dependent studied. The enzyme activity decreased due to heat denaturation of the enzyme with increasing temperature and inactivation time. Inhibition of Thymbra PPO was investigated with inhibitors such as l-cysteine and glutathione using 4-methylcatechol, catechol and pyrogallol as substrates. It was found that l-cysteine was a more effective inhibitor than glutathione owing to lower Ki. The type of inhibition depended on the origin of the PPO studied and also on the substrate used. Furthermore, the IC50 values of inhibitors sudied on PPO were determined by means of activity percentage (I) diagrams. 相似文献
105.
Ozcan Cakmak Huseyin Celik Mehmet Cankurtaran Fuat Buyuklu Nuri Ozgirgin Levent Naci Ozluoglu 《Journal of applied physiology》2003,94(4):1527-1535
We used pipe models to investigate the effects of paranasal sinus ostium size and paranasal sinus volume on the area-distance curves derived by acoustic rhinometry (AR). Each model had a Helmholtz resonator or a short neck as a side branch that simulated the paranasal sinus and sinus ostium. The AR-derived cross-sectional areas posterior to the ostium were significantly overestimated. Sinus volume affected the AR measurements only when the sinus was connected via a relatively large ostium. The experimental area-distance curve posterior to the side branch showed pronounced oscillations in association with low-frequency acoustic resonances in this distal part of the pipe. The experimental results are discussed in terms of theoretically calculated "sound-power reflection coefficients" for the pipe models used. The results indicate that the effects of paranasal sinuses and low-frequency acoustic resonances in the posterior part of the nasal cavity are not accounted for in the current AR algorithms. AR does not provide reliable information about sinus ostium size, sinus volume, or cross-sectional area in the distal parts of nasal cavity. 相似文献
106.
Protective effect of selenium treatment on diabetes-induced myocardial structural alterations 总被引:2,自引:0,他引:2
One of the main causes leading to mortality in diabetes is myocardial disease. Using streptozotocin (STZ)-induced diabetic
animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Interstitial and microvascular disorders
are known to be a characteristic part of the diabetic cardiomyopathy and partly resist insulin therapy. Because diabetic damage
is partly attributed to oxidative stress, antioxidant treatment may be able to reduce this damage. The aim of this study was
to investigate the cardioprotective effect of sodium selenite, known as an antioxidant agent. The diabetes was induced by
ip injection of 50 mg/kg body wt STZ. The duration of diabetes was 5 wk. The protected group received (ip) 5 μmol/kg body
wt/d sodium selenite (Na2SeO3) over 4 wk following diabetes induction. Electron and light microscopic morphometry of heart samples revealed typical diabetic
alterations consisting in an increase in collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration
in myofilaments and Z-lines of myofibers, and myofibrillary degeneration. Sodium selenite treatment could prevent the loss
of myofibrills and reduction of myocyte diameter. In the sodium-selenite-treated diabetic rat heart, alterations of the discus
intercalaris and nucleus were corrected, and degenerations seen in myofilaments and Z-lines were reversed by this treatment.
Under these findings, one can suggest that sodium selenite treatment may alleviate late diabetic complications when it is
used under control conditions. 相似文献
107.
Selenium (Se) has long been recognized as both an essential mammalian nutrient and a hazardous element. Sodium selenite is
commonly used as a dietary supplement for the treatment of Se deficiency. On the other hand, chronic Se toxicity has been
demonstrated to affect the major organs, including the heart, in experimental animals.
This study examines the effects of high concentrations of extracellular selenite (in the range of 0.001–1 mM) application into the recording bath on the electrical properties of rat papillary muscles. Conventional glass semifloating
microelectrodes were used to record intracellular action potentials (APs) in isolated rat papillary muscles. The amplitude
of APs and the resting membrane potential of papillary muscles were not changed following a 20-min selenite (1 mM) application compared to the first minute of its application. Freshly isolated ventricular myocytes by an enzymatic method
were used to determine the selenite-induced alterations in Na+ currents. Na+ currents, measured at 22°C, by the whole-cell patch-clamp technique, decreased by 38±8% in the presence of 1 mM selenite for 5 min. These selenite-induced effects were not reversed, but are restored by dithiothreitol (1 mM).
These results demonstrated that toxic concentrations of selenite induced a significant shortening in AP duration as a result
of an increase in the rate of repolarization. Our findings also suggest that a decrease in Na+ currents, in addition to Ca2+ currents, may play a role in the shortening of AP duration in rat papillary muscles. 相似文献
108.
109.
B. Turan E. Koç Ö. Hotomaroglu E. Kiziltan S. Yildirim E. Demirel 《Biological trace element research》1998,62(3):265-280
In this study, we demonstrated that sodium selenite with high doses (≥ 10-3 M) were potent in inducing a contracture type effect on heart and smooth muscles. Selenite (Se), at a concentration of 10-3
M, caused a contracture effect in heart preparations. Also, low Se concentrations did not have any significant effect. Although
low concentrations of Se (≥ 10-5 M) had a biphasic effects on acetylcholine (ACh) induced and spontaneous ileum contractions, 10-3
M selenite enhanced once more a contracture effect similar to that of the heart preparations. Replacing Ca2+ concentration of the bathing solution by twofold Ca2+ or Ca2+-free did not change the effects of selenite (10-5
M) on contractility of ileum preparations. In vascular smooth muscle, low concentration of selenite (<10-4) had no significant effects on KC1, and phenylephrine-induced contractions and acethylcholineinduced endothelium-dependent
relaxations of isolated rabbit aorta. However, the contractions induced by phenylephrine and the relaxations induced by acetylcholine
in rabbit aorta were depressed significantly by high concentration of selenite (10-3
M). The results obtained by selenite exposure from these three different types of tissue preparations first suggest that the
high concentration of selenite exposure induces some alterations in the functions of muscles and endothelium in a tissue and
dose-dependent manner. Second, this observed irreversible type of dysfunction of tissues induced by l0-3
M selenite is not directly dependent on the Ca2+ entrance into the cytosol, but might be induced by the increase of intracellular Ca2+ with the disturbance of Ca2+ regulation. 相似文献
110.
Selenium (Se), zinc (Zn), copper (Cu), and antioxidant enzyme (superoxide dismutase [SOD] and glutathione peroxidase [GSH-Px]) levels in sera were detected in Behçet patients. Age and sex matched controls were used to find out if oxidative stress takes place in the etiopathogenesis of Behçet’s disease. Superoxide dismutase levels were found to be lower in the whole patients group when compared to controls. In whole patients and inactive patients’ group Zn and Se levels were found to be higher, but not different in the active patients group when compared to controls. No significant difference was found between the groups as Cu and glutathione peroxidase levels were taken into consideration. According to the results of the present study, SOD level is low in Behçet’s disease patients’ sera independent from the phase of the disease, and as a result of decreased SOD activity, increased production of free oxygen radicals may play a role in the etiopathogenesis of the disease. 相似文献