全文获取类型
收费全文 | 2029篇 |
免费 | 136篇 |
专业分类
2165篇 |
出版年
2022年 | 27篇 |
2021年 | 34篇 |
2020年 | 31篇 |
2019年 | 43篇 |
2018年 | 54篇 |
2017年 | 40篇 |
2016年 | 54篇 |
2015年 | 95篇 |
2014年 | 78篇 |
2013年 | 145篇 |
2012年 | 176篇 |
2011年 | 139篇 |
2010年 | 82篇 |
2009年 | 70篇 |
2008年 | 113篇 |
2007年 | 127篇 |
2006年 | 102篇 |
2005年 | 91篇 |
2004年 | 104篇 |
2003年 | 88篇 |
2002年 | 78篇 |
2001年 | 24篇 |
2000年 | 24篇 |
1999年 | 23篇 |
1998年 | 22篇 |
1997年 | 16篇 |
1996年 | 14篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1986年 | 14篇 |
1985年 | 16篇 |
1984年 | 11篇 |
1982年 | 7篇 |
1981年 | 13篇 |
1979年 | 11篇 |
1978年 | 7篇 |
1977年 | 9篇 |
1976年 | 6篇 |
1975年 | 10篇 |
1974年 | 7篇 |
1973年 | 9篇 |
1970年 | 7篇 |
1969年 | 7篇 |
1968年 | 7篇 |
1967年 | 11篇 |
排序方式: 共有2165条查询结果,搜索用时 0 毫秒
31.
Broccolini A Gidaro T De Cristofaro R Morosetti R Gliubizzi C Ricci E Tonali PA Mirabella M 《Journal of neurochemistry》2008,105(3):971-981
Autosomal recessive hereditary inclusion-body myopathy (h-IBM) is caused by mutations of the UDP- N -acetylglucosamine 2-epimerase/ N -acetylmannosamine kinase gene, a rate-limiting enzyme in the sialic acid metabolic pathway. Previous studies have demonstrated an abnormal sialylation of glycoproteins in h-IBM. h-IBM muscle shows the abnormal accumulation of proteins including amyloid-β (Aβ). Neprilysin (NEP), a metallopeptidase that cleaves Aβ, is characterized by the presence of several N-glycosylation sites, and changes in these sugar moieties affect its stability and enzymatic activity. In the present study, we found that NEP is hyposialylated and its expression and enzymatic activity reduced in all h-IBM muscles analyzed. In vitro , the experimental removal of sialic acid by Vibrio Cholerae neuraminidase in cultured myotubes resulted in reduced expression of NEP. This was most likely because of a post-translational modification consisting in an abnormal sialylation of the protein that leads to its reduced stability. Moreover, treatment with Vibrio Cholerae neuraminidase was associated with an increased immunoreactivity for Aβ mainly in the form of distinct cytoplasmic foci within myotubes. We hypothesize that, in h-IBM muscle, hyposialylated NEP has a role in hampering the cellular Aβ clearing system, thus contributing to its abnormal accumulation within vulnerable fibers and possibly promoting muscle degeneration. 相似文献
32.
Amphiphysin II (SH3P9; BIN1), a Member of the Amphiphysin/Rvs Family, Is Concentrated in the Cortical Cytomatrix of Axon Initial Segments and Nodes of Ranvier in Brain and around T Tubules in Skeletal Muscle 总被引:9,自引:2,他引:9 下载免费PDF全文
Margaret Husta Butler Carol David Gian-Carlo Ochoa Zachary Freyberg Laurie Daniell Detlev Grabs Ottavio Cremona Pietro De Camilli 《The Journal of cell biology》1997,137(6):1355-1367
Amphiphysin (amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man syndrome, is a neuronal protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. The yeast homologue of amphiphysin, Rvs167, has pleiotropic functions, including a role in endocytosis and in actin dynamics, suggesting that amphiphysin may also be implicated in the function of the presynaptic actin cytoskeleton. We report here the characterization of a second mammalian amphiphysin gene, amphiphysin II (SH3P9; BIN1), which encodes products primarily expressed in skeletal muscle and brain, as differentially spliced isoforms. In skeletal muscle, amphiphysin II is concentrated around T tubules, while in brain it is concentrated in the cytomatrix beneath the plasmamembrane of axon initial segments and nodes of Ranvier. In both these locations, amphiphysin II is colocalized with splice variants of ankyrin3 (ankyrinG), a component of the actin cytomatrix. In the same regions, the presence of clathrin has been reported. These findings support the hypothesis that, even in mammalian cells, amphiphysin/Rvs family members have a role both in endocytosis and in actin function and suggest that distinct amphiphysin isoforms contribute to define distinct domains of the cortical cytoplasm. Since amphiphysin II (BIN1) was reported to interact with Myc, it may also be implicated in a signaling pathway linking the cortical cytoplasm to nuclear function. 相似文献
33.
Cataldi A Centurione L Di Pietro R Rapino M Bosco D Grifone G Garaci F Rana R 《Journal of cellular biochemistry》2003,88(1):144-151
Friend erythroleukemia cells require high doses (15 Gy) of ionizing radiation to display a reduced rate of proliferation and an increased number of dead cells. Since ionizing radiation can activate several signaling pathways at the plasma membrane which can lead to the nuclear translocation of a number of proteins, we looked at the intranuclear signaling system activated by Protein Kinases C, being this family of enzymes involved in the regulation of cell growth and death. Our results show an early and dose-dependent increased activity of zeta and epsilon isoforms, although PKC zeta is the only isoform significantly active and translocated into the nuclear compartment upon low (1.5 Gy) and high (15 Gy) radiation doses. These observations are concomitant and consistent with an increase in the anti-apoptotic protein Bcl-2 level upon both radiation doses. Our results point at the involvement of the PKC pathway in the survival response to ionizing radiation of this peculiar cell line, offering PKC zeta for consideration as a possible target of pharmacological treatments aimed at amplifying the effect of such a genotoxic agent. 相似文献
34.
Carlo Capelli Guglielmo Antonutto Paola Zamparo Massimo Girardis Pietro Enrico di Prampero 《European journal of applied physiology and occupational physiology》1993,66(3):189-195
The mechanical power (Wtot, W·kg–1) developed during ten revolutions of all-out periods of cycle ergometer exercise (4–9 s) was measured every 5–6 min in six subjects from rest or from a baseline of constant aerobic exercise [50%–80% of maximal oxygen uptake (VO2max)] of 20–40 min duration. The oxygen uptake [VO2 (W·kg–1, 1 ml O2 = 20.9 J)] and venous blood lactate concentration ([la]b, mM) were also measured every 15 s and 2 min, respectively. During the first all-out period, Wtot decreased linearly with the intensity of the priming exercise (Wtot = 11.9–0.25·VO2). After the first all-out period (i greater than 5–6 min), and if the exercise intensity was less than 60% VO2max, Wtot, VO2 and [la]b remained constant until the end of the exercise. For exercise intensities greater than 60% VO2max, VO2 and [la]b showed continuous upward drifts and Wtot continued decreasing. Under these conditions, the rate of decrease of Wtot was linearly related to the rate of increase of V [(d Wtot/dt) (W·kg–1·s–1) = 5.0·10–5 –0.20·(d VO2/dt) (W·kg–1·s–1)] and this was linearly related to the rate of increase of [la]b [(d VO2/dt) (W·kg–1·s–1) = 2.310–4 + 5.910–5·(d [la]b/dt) (mM·s–1)]. These findings would suggest that the decrease of Wtot during the first all-out period was due to the decay of phosphocreatine concentration in the exercising muscles occurring at the onset of exercise and the slow drifts of VO2 (upwards) and of Wtot (downwards) during intense exercise at constant Wtot could be attributed to the continuous accumulation of lactate in the blood (and in the working muscles). 相似文献
35.
Abstract Original material of the 12 taxa described as new by Bertoloni has been examined, and typification of their names is discussed. Lectotypes are designated for 11 of Bertoloni's names, one (O. densiflora Bertol.) had been lectotypified before. Orobanche bicolor Bertol. (non C. A. Mey.) belongs to O. cernua L., O. cruenta Bertol. to O. gracilis Sm., O. stricta Moris ex Bertol. to O. schultzii Mutel, O. thyrsoidea Moris ex Bertol to O. rigens Loisel., O. crithmi Bertol. to O. minor Sm., O. vitalbae Bertol. to O. artemisiae-campestris Gaudin, O. fragrantissima Bertol. to O. lutea Baumg., O. laurina Bertol. to O. hederae Duby, O. yuccae Savi f. ex Bertol. to O. hederae Duby (not to O. minor Sm.), O. centaurina Bertol. to O. litorea Guss. (not to O. artemisiae-campestris Gaudin). O. australis Moris ex Bertol., included by Beck in O. canescens C. Presl, is a good species restricted to Sardinia. O. densiflora Bertol. must not, as is customary, be ascribed to Reuter who republished it later. 相似文献
36.
Glacial habitats (cryosphere) include some of the largest unexplored and extreme biospheres on Earth. These habitats harbor a wide diversity of psychrophilic prokaryotic and eukaryotic microorganisms. These highly specialized microorganisms have developed adaptation strategies to overcome the direct and indirect life-endangering influence of low temperatures. For many years Antarctica has been the geographic area preferred by microbiologists for studying the diversity of psychrophilic microorganisms (including yeasts). However, there have been an increasing number of studies on psychrophilic yeasts sharing the non-Antarctic cryosphere. The present paper provides an overview of the distribution and adaptation strategies of psychrophilic yeasts worldwide. Attention is also focused on their biotechnological potential, especially on their exploitation as a source of cold-active enzymes and for bioremediation purposes. 相似文献
37.
Giovanni Pennisi Giuseppe Lanza Salvatore Giuffrida Luisa Vinciguerra Valentina Puglisi Mariagiovanna Cantone Manuela Pennisi Carmela Cinzia D'Agate Pietro Naso Giuseppe Aprile Giulia Malaguarnera Raffaele Ferri Rita Bella 《PloS one》2014,9(7)
Introduction
Celiac disease (CD) may initially present as a neurological disorder or may be complicated by neurological changes. To date, neurophysiological studies aiming to an objective evaluation of the potential central nervous system involvement in CD are lacking.Objective
To assess the profile of cortical excitability to Transcranial Magnetic Stimulation (TMS) in a group of de novo CD patients.Materials and methods
Twenty CD patients underwent a screening for cognitive and neuropsychiatric symptoms by means of the Mini Mental State Examination and the Structured Clinical Interview for DSM-IV Axis I Disorders, respectively. Instrumental exams, including electroencephalography and brain computed tomography, were also performed. Cortico-spinal excitability was assessed by means of single and paired-pulse TMS using the first dorsal interosseus muscle of the dominant hand. TMS measures consisted of resting motor threshold, motor evoked potentials, cortical silent period (CSP), intracortical inhibition (ICI) and facilitation (ICF). None of the CD was on gluten-free diet. A group of 20 age-matched healthy controls was used for comparisons.Results
CD showed a significantly shorter CSP (78.0 vs 125.0 ms, p<0.025), a reduced ICI (0.3 vs 0.2, p<0.045) and an enhanced ICF (1.1 vs 0.7, p<0.042) compared to controls. A dysthymic disorder was identified in five patients. The effect size between dysthymic and non-dysthymic CD patients indicated a low probability of interference with the CSP (Cohen''s d -0.414), ICI (-0.278) and ICF (-0.292) measurements.Conclusion
A pattern of cortical excitability characterized by “disinhibition” and “hyperfacilitation” was found in CD patients. Immune system dysregulation might play a central role in triggering changes of the motor cortex excitability. 相似文献38.
Lucia Monti Donatella Donati Elisabetta Menci Samuele Cioni Matteo Bellini Irene Grazzini Sara Leonini Paolo Galluzzi Sauro Severi Luca Burroni Alfredo Casasco Lucia Morbidelli Emiliano Santarnecchi Pietro Piu 《PloS one》2015,10(2)
Literature has suggested that changes in brain flow circulation occur in patients with multiple sclerosis. In this study, digital subtraction angiography (DSA) was used to measure the absolute CCT value in MS patients and to correlate its value to age at disease onset and duration, and to expand disability status scale (EDSS). DSA assessment was performed on eighty MS patients and on a control group of forty-four age-matched patients. CCT in MS and control groups was calculated by analyzing the angiographic images. Lesion and brain volumes were calculated in a representative group of MS patients. Statistical correlations among CCT and disease duration, age at disease onset, lesion load, brain volumes and EDSS were considered. A significant difference between CCT in MS patients (mean = 4.9s; sd = 1.27s) and control group (mean = 2.8s; sd = 0.51s) was demonstrated. No significant statistical correlation was found between CCT and the other parameters in all MS patients. Significantly increased CCT value in MS patients suggests the presence of microvascular dysfunctions, which do not depend on clinical and MRI findings. Hemodynamic changes may not be exclusively the result of a late chronic inflammatory process. 相似文献
39.
Mauro Musto Daniele Cardinale Pietro Lucia Daniela Faraone 《Journal of applied animal welfare science : JAAWS》2016,19(3):217-233
This study evaluated whether showing a video of the different ways of raising goats for milk affected consumer acceptability. Four combinations, 2 Videos (intensive [INT] and semiextensive [SEM] system) × 2 Milk Types (semiskimmed [S] and whole [W] milk), were evaluated by 70 habitual consumers of goat milk, who scored their liking and purchase intention during blind (B), expected (E), and informed (I) acceptability sessions. In the B session, consumers tasted both milk types without information. S samples were preferred over W samples. In the E session, SEM video created high expectations in terms of milk liking and purchase intent, whereas the opposite happened when showing INT video. In the I session, consumers showed a clear preference for combinations created using SEM video, regardless of milk type. W-SEM and S-INT were worse (negative disconfirmation) and better (positive disconfirmation) than expected, respectively. A complete assimilation toward expectations occurred only for S-INT. INT video adversely affected the acceptability of S samples. Concerning purchase intent, W-SEM and S-SEM were worse than expected, but the assimilation was complete only for S-SEM: SEM video increased purchase intent for S samples. 相似文献
40.