全文获取类型
收费全文 | 337篇 |
免费 | 24篇 |
出版年
2024年 | 2篇 |
2023年 | 13篇 |
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 18篇 |
2019年 | 11篇 |
2018年 | 14篇 |
2017年 | 10篇 |
2016年 | 19篇 |
2015年 | 19篇 |
2014年 | 26篇 |
2013年 | 19篇 |
2012年 | 20篇 |
2011年 | 25篇 |
2010年 | 17篇 |
2009年 | 6篇 |
2008年 | 22篇 |
2007年 | 23篇 |
2006年 | 15篇 |
2005年 | 13篇 |
2004年 | 5篇 |
2003年 | 5篇 |
2002年 | 2篇 |
2001年 | 4篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
1962年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有361条查询结果,搜索用时 23 毫秒
101.
Dilek Arpaci Sevim Karakas Celik Murat Can Esra Ermiş Fatih Kuzu Furuzan Kokturk 《Redox report : communications in free radical research》2013,18(6):281-286
Background: Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly.Methods: A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined.Results: No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P?>?0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P?=?0.007). The median serum PON level was 101?±?63.36?U/l in the case group and 63?±?60.50?U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P?=?0.004, r?=?0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P?=?0.607 and P?=?0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P?=?0.385), nor between those with PON1 L55M and Q192R polymorphisms (P?=?0.161 and P?=?0.336, respectively).Conclusions: Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters. 相似文献
102.
Unal Esra Aslan Ezgi Irmak Ozturk Tulin Kurnaz Gomleksiz Ozlem Kucukhuseyin Ozlem Tuzuner M. Bora Seyhan M. Fatih Ozturk Oguz Yilmaz Aydogan Hulya 《Biochemical genetics》2021,59(6):1413-1426
103.
Roan E Waters CM 《American journal of physiology. Lung cellular and molecular physiology》2011,301(5):L625-L635
The pulmonary alveolus, terminal gas-exchange unit of the lung, is composed of alveolar epithelial and endothelial cells separated by a thin basement membrane and interstitial space. These cells participate in the maintenance of a delicate system regulated not only by biological factors but also by the mechanical environment of the lung, which undergoes dynamic deformation during breathing. Clinical and animal studies as well as cell culture studies point toward a strong influence of mechanical forces on lung cells and tissues including effects on growth and repair, surfactant release, injury, and inflammation. However, despite substantial advances in our understanding of lung mechanics over the last half century, there are still many unanswered questions regarding the micromechanics of the alveolus and how it deforms during lung inflation. Therefore, the aims of this review are to draw a multidisciplinary account of the mechanics of the alveolus on the basis of its structure, biology, and chemistry and to compare estimates of alveolar deformation from previous studies. 相似文献
104.
The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape. In previous theoretical studies we have investigated the regimes of linear instability where spontaneous formation of cellular protrusions is initiated. Here we calculate the evolution of a two dimensional cell contour beyond the linear regime and determine the final steady-state shapes arising within the model. We find that shapes driven by adhesion or by actin polymerization (lamellipodia) have very different morphologies, as observed in cells. Furthermore, we find that as the strength of the protrusive forces diminish, the system approaches a stabilization of a periodic pattern of protrusions. This result can provide an explanation for a number of puzzling experimental observations regarding cellular shape dependence on the properties of the extra-cellular matrix. 相似文献
105.
Yoel P. Ohayon Arun Richard Chandrasekaran Esra Demirel Sabrine I. Obbad Rutu C. Shah Victoria T. Adesoba 《Journal of biomolecular structure & dynamics》2013,31(1):84-85
Our laboratory has reported a self-assembled 3-D crystal based on a DNA tensegrity triangle. The tensegrity triangle is a rigid DNA motif with three-fold rotational symmetry consisting of three helices whose axes are directed along three linearly independent directions (1). The triangles form a crystalline lattice stabilized via sticky ends (2). The length of the sticky ends reported previously was two nucleotides (nt) GA:TC. Although diffracting to 4 Å resolution at the APS-ID19 beam line, they diffract only to 4.9 Å at the NSLS-X25 beam line. In the current study, we have analysed the effect of sticky end length and sequence on crystal formation and the resolution of the X-ray diffraction pattern on NSLS-X25. Tensegrity triangle motifs having 1-, 2-, and 3-nt sticky ends have all formed crystals. X-ray diffraction data from the same beam line revealed that the crystal resolution was somewhat better for the 2-nt sticky end having an AA:TT base pair (4.75 Å) than GA:CT and CC:GG (8.0 Å). Moreover, the 1-nt sticky end (C:G) yielded a diffraction pattern whose resolution (3.5 Å) compared favorably with all the three 2-nt sticky end systems. However, the triangle motif having a 1-nt sticky end with an A:T base pair did not yield any crystals. For motifs with 3-nt sticky ends, the sequence GAG:CTC produced small crystals (10–20?μm), while larger crystals (150?μm) were obtained with the sequences TAG:ATC and TAT:ATA. Our results indicate that not only do the lengths and sequences of the sticky ends define the interactions between motifs, but they also have an impact on the resulting resolution. We expect redesigned assemblies to form 3-D crystals with better resolution that can aid in the scaffolding of biological macromolecules for crystallographic structure determination. Applications in many areas of DNA nanotechnology are expected to benefit from a complete analysis of the effects of sticky end length, sequence, and free energy. 相似文献
106.
107.
Erol Saygili Patrick Schauerte Maimouna Pekassa Esra Saygili Gediminas Rackauskas Robert H. G. Schwinger Joachim Weis Christian Weber Nikolaus Marx Obaida R. Rana 《Cellular and molecular neurobiology》2011,31(1):17-25
Recently, we have shown that high frequency electrical field stimulation (HFES) of sympathetic neurons (SN) induces nerve
sprouting by up-regulation of nerve growth factor (NGF) which targets the tyrosine kinase A receptor (TrkA) in an autocrine/paracrine
manner. There is increasing evidence that matrix metalloproteinase-2 (MMP-2) is not only involved in extracellular matrix
(ECM) turnover but may also exert beneficial effects during neuronal growth. Therefore, this study aimed to investigate the
regulation and function of MMP-2 and its major activator membrane type 1-matrix metalloproteinase (MT1-MMP) as well its inhibitor
TIMP-1 in SN under conditions of HFES. Moreover, we analyzed molecular mechanisms of the beneficial effect of losartan, an
angiotensin II type I receptor (AT-1)blocker on HFES-induced nerve sprouting. Cell cultures of SN from the superior cervical
ganglia (SCG) of neonatal rats were electrically stimulated for 48 h with a frequency of 5 or 50 Hz. HFES increased MMP-2
and MT1-MMP mRNA and protein expression, whereas TIMP-1 expression remained unchanged. Under conditions of HFES, we observed
a shift from pro- to active-MMP-2 indicating an increase in MMP-2 enzyme activity. Specific pharmacological MMP-2 inhibition
contributed to an increase in pro-NGF amount in the cell culture supernatant and significantly reduced HFES-induced neurite
outgrowth. Losartan abolished HFES-induced nerve sprouting in a significant manner by preventing HFES-induced NGF, MMP-2,
and MT1-MMP up-regulation. In summary, specific MMP-2 blockade prevents sympathetic nerve sprouting (SNS) by inhibition of
pro-NGF conversion while losartan abolishes HFES-induced SNS by reducing total NGF, MMP-2 and MT1-MMP expression. 相似文献
108.
Oktem F Kirbas A Armagan A Kuybulu AE Yilmaz HR Ozguner F Uz E 《Molecular and cellular biochemistry》2011,357(1-2):247-253
Genetic factors related to cancer have been extensively studied and several polymorphisms have been associated to breast cancer. The FGFR4, MTHFR, and HFE genes have been associated with neoplastic diseases development. The current report outlines the analysis of the polymorphisms G388A (FGFR4), C677T (MTHFR), C282Y, and H63D (HFE) in Brazilian breast cancer patients. We studied 68 patients with invasive ductal and operable breast carcinoma and 85 women as a control group. The polymorphism frequencies in the breast cancer and control groups were analyzed, but no significant difference was observed by comparing the two groups. The presence of each polymorphism was analyzed according to the clinical features and markers already established as prognostic in the breast cancer group. The C677T, H63D, and G388A polymorphisms were not associated to histological grade, age of diagnosis, expression of HER2 receptor, or estrogen and progesterone receptor. The H63D polymorphism showed a significant association (P = 0.02) with the presence of p53 mutations, and C667T showed association to lymph node involvement (P = 0.05). Lymph node involvement, G388A polymorphism, and histological grade were independently associated to metastasis/death. Our data suggests that the polymorphisms G388A, C677T, and H63D are not useful in breast cancer diagnosis, but they may be significant additional prognostic markers related to breast cancer survival. 相似文献
109.
Tissue specialization at the metabolite level is perceived during the development of tomato fruit 总被引:4,自引:0,他引:4
Moco S Capanoglu E Tikunov Y Bino RJ Boyacioglu D Hall RD Vervoort J De Vos RC 《Journal of experimental botany》2007,58(15-16):4131-4146
Fruit maturation and tissue differentiation are important topics in plant physiology. These biological phenomena are accompanied by specific alterations in the biological system, such as differences in the type and concentration of metabolites. The secondary metabolism of tomato (Solanum lycopersicum) fruit was monitored by using liquid chromatography (LC) coupled to photo-diode array (PDA) detection, fluorescence detection (FD), and mass spectrometry (MS). Through this integrated approach different classes of compounds were analysed: carotenoids, xanthophylls, chlorophylls, tocopherols, ascorbic acid, flavonoids, phenolic acids, glycoalkaloids, saponins, and other glycosylated derivatives. Related metabolite profiles of peel and flesh were found between several commercial tomato cultivars indicating similar metabolite trends despite the genetic background. For a single tomato cultivar, metabolite profiles of different fruit tissues (vascular attachment region, columella and placenta, epidermis, pericarp, and jelly parenchyma) were examined at the green, breaker, turning, pink, and red stages of fruit development. Unrelated to the chemical nature of the metabolites, behavioural patterns could be assigned to specific ripening stages or tissues. These findings suggest spatio-temporal specificity in the accumulation of endogenous metabolites from tomato fruit. 相似文献
110.
Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4 总被引:2,自引:1,他引:1 下载免费PDF全文
Stendel C Roos A Deconinck T Pereira J Castagner F Niemann A Kirschner J Korinthenberg R Ketelsen UP Battaloglu E Parman Y Nicholson G Ouvrier R Seeger J De Jonghe P Weis J Krüttgen A Rudnik-Schöneborn S Bergmann C Suter U Zerres K Timmerman V Relvas JB Senderek J 《American journal of human genetics》2007,81(1):158-164
GTPases of the Rho subfamily are widely involved in the myelination of the vertebrate nervous system. Rho GTPase activity is temporally and spatially regulated by a set of specific guanine nucleotide exchange factors (GEFs). Here, we report that disruption of frabin/FGD4, a GEF for the Rho GTPase cell-division cycle 42 (Cdc42), causes peripheral nerve demyelination in patients with autosomal recessive Charcot-Marie-Tooth (CMT) neuropathy. These data, together with the ability of frabin to induce Cdc42-mediated cell-shape changes in transfected Schwann cells, suggest that Rho GTPase signaling is essential for proper myelination of the peripheral nervous system. 相似文献