全文获取类型
收费全文 | 561篇 |
免费 | 26篇 |
国内免费 | 1篇 |
出版年
2023年 | 7篇 |
2022年 | 12篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 15篇 |
2015年 | 23篇 |
2014年 | 32篇 |
2013年 | 27篇 |
2012年 | 35篇 |
2011年 | 36篇 |
2010年 | 25篇 |
2009年 | 16篇 |
2008年 | 33篇 |
2007年 | 32篇 |
2006年 | 25篇 |
2005年 | 23篇 |
2004年 | 19篇 |
2003年 | 36篇 |
2002年 | 24篇 |
2001年 | 8篇 |
2000年 | 10篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1997年 | 10篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1986年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1968年 | 3篇 |
1962年 | 2篇 |
1933年 | 1篇 |
1930年 | 1篇 |
排序方式: 共有588条查询结果,搜索用时 15 毫秒
11.
12.
Vadim Danilov Nina Baranova Anvar Ismailov Nicolai Egorov 《Applied microbiology and biotechnology》1982,14(2):125-129
Summary The inhibitory effect of camphor on bioluminescence of both bacteria and bacterial luciferase has been examined. The camphor has been shown to be a substrate of cytochrome P-450 of the luminous bacteria Photobacterium fischeri. The inhibition of the luminescence reaction provided evidence for the competitive nature of the interaction of camphor and aliphatic aldehyde at the binding site for luciferase. Camphor is also supposed to interact with P-450. The findings indicate that the hydroxylation process of camphor affects the kinetics of the luminescence. 相似文献
13.
This paper describes a mathematical model for the enzymatic hydrolysis and fermentation of cellulose by Trichoderma reesei. The principal features of the model are the assumption of two forms of cellulose (crystalline and amorphous), two sugars (cellobiose and glucose), and two enzymes (cellulase and β-glucosidase). An inducer–repressor–messenger RNA mechanism is used to predict enzyme formation, and pH effects are included. The model consists of 12 ordinary differential equations for 12 state variables and contains 38 parameters. The parameters were estimated from four sets of experimental data by optimization. The results appear satisfactory, and the computer programs permit simulation of a variety of system changes. 相似文献
14.
Kim Tallaksen Halvorsen Torkel Larsen Howard I. Browman Caroline Durif Nicolai Aasen Leif Asbjørn Vøllestad Alessandro Cresci Tonje Knutsen Sørdalen Reidun M. Bjelland Anne Berit Skiftesvik 《Journal of fish biology》2021,99(4):1513-1518
The movement patterns of three commercially important wrasse (Labridae) species inside a small marine protected area (~ 0.15 km2) on the west coast of Norway were analysed over a period of 21 months. The mean distance between capture and recapture locations varied between 10 and 187 m, and was species and season specific. The extent of movement was not related to body size or sex. These results imply that a network of small strategically located marine protected areas can be used as management tools to protect wrasses from size- and sex-selective fishing mortality. 相似文献
15.
Joana M. Andrade Eva María Domínguez-Martín Marisa Nicolai Clia Faustino Luís Monteiro Rodrigues Patrícia Rijo 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):258
A series of Plectranthus spp. plant extracts (aqueous, acetonic, methanolic and ethyl acetic) obtained from eight different species, and previously isolated compounds (ranging from polyphenols, diterpenes and triterpenes), were assayed for in vitro inhibition of the skin-related enzymes tyrosinase, collagenase and elastase, and for studying their antioxidant properties. The ethyl acetic extracts of P. grandidentatus and P. ecklonii registered the highest antioxidant activity, whereas acetonic, methanolic and ethyl acetic extracts of P. ecklonii, P. grandidentatus, P. madagascariensis and P. saccatus concerning the enzymatic inhibition assays revealed high anti-tyrosinase and anti-collagenase activities. From the isolated compounds tested, abietane diterpenes and triterpenes were highly active against tyrosinase and elastase activity. Overall, the experimental results showed the powerful antioxidant and inhibitory action on skin-related enzymes tyrosinase, collagenase and elastase of Plectranthus spp. extracts and/or isolated compounds, supporting their further research as bioactive metabolites against skin sagging and hyperpigmentation in cosmetic and pharmaceutical formulations. 相似文献
16.
Isabella Werner Fengwei Guo Nicolai V. Bogert Ulrich A. Stock Patrick Meybohm Anton Moritz Andres Beiras-Fernandez 《PloS one》2013,8(12)
Vasoplegia is a severe complication after cardiac surgery. Within the last years the administration of nitric oxide synthase inhibitor methylene blue (MB) became a new therapeutic strategy. Our aim was to investigate the role of MB on transendothelial migration of circulating blood cells, the potential role of cyclic cGMP, eNOS and iNOS in this process, and the influence of MB on endothelial cell apoptosis. Human vascular endothelial cells (HuMEC-1) were treated for 30 minutes or 2 hours with different concentrations of MB. Inflammation was mimicked by LPS stimulation prior and after MB. Transmigration of PBMCs and T-Lymphocytes through the treated endothelial cells was investigated. The influence of MB upon the different subsets of PBMCs (Granulocytes, T- and B-Lymphocytes, and Monocytes) was assessed after transmigration by means of flow-cytometry. The effect of MB on cell apoptosis was evaluated using Annexin-V and Propidium Iodide stainings. Analyses of the expression of cyclic cGMP, eNOS and iNOS were performed by means of RT-PCR and Western Blot. Results were analyzed using unpaired Students T-test. Analysis of endothelial cell apoptosis by MB indicated a dose-dependent increase of apoptotic cells. We observed time- and dose-dependent effects of MB on transendothelial migration of PBMCs. The prophylactic administration of MB led to an increase of transendothelial migration of PBMCs but not Jurkat cells. Furthermore, HuMEC-1 secretion of cGMP correlated with iNOS expression after MB administration but not with eNOS expression. Expression of these molecules was reduced after MB administration at protein level. This study clearly reveals that endothelial response to MB is dose- and especially time-dependent. MB shows different effects on circulating blood cell-subtypes, and modifies the release patterns of eNOS, iNOS, and cGMP. The transendothelial migration is modulated after treatment with MB. Furthermore, MB provokes apoptosis of endothelial cells in a dose/time-dependent manner. 相似文献
17.
Eugenia M. Rapoport Ekaterina V. Moiseeva Dmitry A. Aronov Sergey V. Khaidukov Galina V. Pazynina Svetlana V. Tsygankova Ivan M. Ryzhov Ivan M. Belyanchikov Tatiana V. Tyrtysh Kenneth C. McCullough Nicolai V. Bovin 《Glycoconjugate journal》2020,37(1):129-138
Modification of vaccine carriers by decoration with glycans can enhance binding to and even targeting of dendritic cells (DCs), thus augmenting vaccine efficacy. To find a specific glycan-“vector” it is necessary to know glycan-binding profile of DCs. This task is not trivial; the small number of circulating blood DCs available for isolation hinders screening and therefore advancement of the profiling. It would be more convenient to employ long-term cell cultures or even primary DCs from murine blood. We therefore examined whether THP-1 (human monocyte cell line) and DC2.4 (immature murine DC-like cell line) could serve as a model for human DCs. These cells were probed with a set of glycans previously identified as binding to circulating human CD14low/-CD16+CD83+ DCs. In addition, we tested a subpopulation of murine CD14low/-CD80+СD11c+CD16+ cells reported as relating to the human CD14low/-CD16+CD83+ cells. Manα1–3(Manα1–6)Manβ1–4GlcNAcβ1–4GlcNAcβ bound to both the cell lines and the murine CD14low/-CD80+СD11c+CD16+ cells. Primary cells, but not the cell cultures, were capable of binding GalNAcα1–3Galβ (Adi), the most potent ligand for binding to human circulating DCs. In conclusion, not one of the studied cell lines proved an adequate model for DCs processes involving lectin binding. Although the glycan-binding profile of BYRB-Rb (8.17)1Iem mouse DCs could prove useful for assessing human DCs, important glycan interactions were missing, a situation which was aggravated when employing cells from the BALB/c strain. Accordingly, one must treat results from murine work with caution when seeking vaccine targeting of human DCs, and certainly should avoid cell lines such as THP-1 and DC2.4 cells. 相似文献
18.
Gitte Hedermann Christoffer Rasmus Vissing Karen Heje Nicolai Preisler Nanna Witting John Vissing 《PloS one》2016,11(1)
Introduction
Congenital myopathies (CM) often affect contractile proteins of the sarcomere, which could render patients susceptible to exercise-induced muscle damage. We investigated if exercise is safe and beneficial in patients with CM.Methods
Patients exercised on a stationary bike for 30 minutes, three times weekly, for 10 weeks at 70% of their maximal oxygen uptake (VO2max). Creatine kinase (CK) was monitored as a marker of muscle damage. VO2max, functional tests, and questionnaires evaluated efficacy.Results
Sixteen patients with CM were included in a controlled study. VO2max increased by 14% (range, 6–25%; 95% CI 7–20; p < 0.001) in the seven patients who completed training, and tended to decrease in a non-intervention group (n = 7; change -3.5%; range, -11–3%, p = 0.083). CK levels were normal and remained stable during training. Baseline Fatigue Severity Scale scores were high, 4.9 (SE 1.9), and tended to decrease (to 4.4 (SE 1.7); p = 0.08) with training. Nine patients dropped out of the training program. Fatigue was the major single reason.Conclusions
Ten weeks of endurance training is safe and improves fitness in patients with congenital myopathies. The training did not cause sarcomeric injury, even though sarcomeric function is affected by the genetic abnormalities in most patients with CM. Severe fatigue, which characterizes patients with CM, is a limiting factor for initiating training in CM, but tends to improve in those who train.Trial Registration
The Regional Committee on Health Research Ethics of the Capital Region of Denmark H-2-2013-066 and ClinicalTrials.gov H2-2013-066 相似文献19.
Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin 下载免费PDF全文
Valentina De Lorenzi Gian Maria Sarra Ferraris Jeppe B Madsen Michela Lupia Peter A Andreasen Nicolai Sidenius 《EMBO reports》2016,17(7):982-998
Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI‐1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR. Moreover, we show that PAI‐1 counteracts the negative feedback and behaves as a proteolysis‐triggered stabilizer of uPAR‐mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N‐terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. 相似文献
20.
Proteolytic cleavage of the Chlamydia pneumoniae major outer membrane protein in the absence of Pmp10 总被引:1,自引:0,他引:1
The genome of the obligate intracellular bacteria Chlamydia pneumoniae contains 21 genes encoding polymorphic membrane proteins (Pmp). While no function has yet been attributed to the Pmps, they may be involved in an antigenic variation of the Chlamydia surface. It has previously been demonstrated that Pmp10 is differentially expressed in the C. pneumoniae CWL029 isolate. To evaluate whether the absence of Pmp10 in the outer membrane causes further changes to the C. pneumoniae protein profile, we subcloned the CWL029 isolate and selected a clone with minimal Pmp10 expression. Subsequently, we compared the proteome of the CWL029 isolate with the proteome of the subcloned strain and identified a specific cleavage of the C-terminal part of the major outer membrane protein (MOMP), which occurred only in the absence of Pmp10. In contrast, when Pmp10 was expressed we predominantly observed full-length MOMP. No other proteins appeared to be regulated according to the presence or absence of Pmp10. These results suggest a close association between MOMP and Pmp10, where Pmp10 may protect the C-terminal part of MOMP from proteolytic cleavage. 相似文献