全文获取类型
收费全文 | 909篇 |
免费 | 47篇 |
国内免费 | 4篇 |
出版年
2024年 | 2篇 |
2023年 | 10篇 |
2022年 | 29篇 |
2021年 | 35篇 |
2020年 | 20篇 |
2019年 | 23篇 |
2018年 | 41篇 |
2017年 | 23篇 |
2016年 | 33篇 |
2015年 | 46篇 |
2014年 | 55篇 |
2013年 | 75篇 |
2012年 | 59篇 |
2011年 | 93篇 |
2010年 | 68篇 |
2009年 | 46篇 |
2008年 | 70篇 |
2007年 | 47篇 |
2006年 | 24篇 |
2005年 | 36篇 |
2004年 | 34篇 |
2003年 | 19篇 |
2002年 | 17篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
排序方式: 共有960条查询结果,搜索用时 15 毫秒
81.
Sidi AO Babah KO Brimer N Nominé Y Romier C Kieffer B Pol SV Travé G Zanier K 《Protein expression and purification》2011,80(1):8-16
E6 is a small oncoprotein involved in tumorigenesis induced by papillomaviruses (PVs). E6 often recognizes its cellular targets by binding to short motifs presenting the consensus LXXLL. E6 proteins have long resisted structural analysis. We found that bovine papillomavirus type 1 (BPV1) E6 binds the N-terminal LXXLL motif of the cellular protein paxillin with significantly higher affinity as compared to other E6/peptide interactions. Although recombinant BPV1 E6 was poorly soluble in the free state, provision of the paxillin LXXLL peptide during BPV1 E6 biosynthesis greatly enhanced the protein's solubility. Expression of BPV1 E6/LXXLL peptide complexes was carried out in bacteria in the form of triple fusion constructs comprising, from N- to C-terminus, the soluble carrier protein maltose binding protein (MBP), the LXXLL motif and the E6 protein. A TEV protease cleavage site was placed either between MBP and LXXLL motif or between LXXLL motif and E6. These constructs allowed us to produce highly concentrated samples of BPV1 E6, either covalently fused to the C-terminus of the LXXLL motif (intra-molecular complex) or non-covalently bound to it (inter-molecular complex). Heteronuclear NMR measurements were performed and showed that the E6 protein was folded with similar conformations in both covalent and non-covalent complexes. These data open the way to novel structural and functional studies of the BPV1 E6 in complex with its preferential target motif. 相似文献
82.
Bustanji Y Al-Masri IM Mohammad M Hudaib M Tawaha K Tarazi H Alkhatib HS 《Journal of enzyme inhibition and medicinal chemistry》2011,26(4):453-459
The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few drugs are currently available on the market. In the present study, the methanolic extract of Ginkgo biloba L. (Ginkgoaceae) was investigated as an inhibitor of pancreatic lipase (PL) in an attempt to explain its hypolipidaemic activity. In vitro assay of G. biloba leaves extract revealed a substantial PL inhibition activity (IC(50)?=?16.5 μg/mL). Further investigation was performed by employing theoretical docking simulations and experimental testing to uncover the active constituents responsible for G. biloba anti-lipase activity. Virtually, terpene trilactones, including ginkgolides and bilobalide, were found to fit within the binding pocket of PL via several attractive interactions with key amino acids. Experimentally, ginkgolides A, B, and bilobalide were found to inhibit PL significantly (IC(50)?=?22.9, 90.0, and 60.1 μg/mL, respectively). Our findings demonstrated that the hypolipidaemic effects of G. biloba extract can be attributed to the inhibition of PL by, at least in part, terpene trilactones. In conclusion, this work can be considered a new step towards the discovery of new natural safe hypolipidaemic PL inhibitors. 相似文献
83.
Equilibrium unfolding by guanidinium hydrochloride (GuHCl) and urea as well as evolutionary trends of two homologous albumins,
pig serum albumin (PSA) and rabbit serum albumin (RSA), has been studied with circular dichroism, tryptophanyl fluorescence
and bioinformatics. GuHCl cannot distinguish the contribution of electrostatic interactions to the proteins which were otherwise
effectively monitored by urea. Higher differences in free energy changes due to urea than GuHCl show electrostatic interactions
among charged amino acids are possibly responsible for higher structural stability of RSA in comparison to PSA. From the sequence
of HSA and RSA, deletion of arginine at position 117 and the presence of one extra tryptophan at position 135 may possess
some clue for lesser stability of PSA. Here, for comparison, chemical unfolding data of HSA and BSA had been taken into consideration.
We found that thermodynamically RSA and PSA are closer to HSA and BSA, respectively, in accordance with their sequence homologies.
Taxonomically, rabbit belongs to lagomorph which is closer to hominids than ungulates. Hence, on the basis of these thermodynamic
data of protein denaturation of different species we can use this new approach to analyze the phylogenetic relationship among
the major clades of eutherian mammals to obtain their evolutionary trends. 相似文献
84.
Soudani N Ben Amara I Troudi A Hakim A Bouaziz H Ayadi Makni F Zeghal KM Zeghal N 《Journal of physiology and biochemistry》2011,67(4):577-588
Excess chromium (Cr) exposure is associated with various pathological conditions including hematological dysfunction. The
generation of oxidative stress is one of the plausible mechanisms behind Cr-induced cellular deteriorations. The efficacy
of selenium (Se) to combat Cr-induced oxidative damage in the erythrocytes of adult rats was investigated in the current study.
Female Wistar rats were randomly divided into four groups of six each: group I served as controls which received standard
diet, group II received in drinking water K2Cr2O7 alone (700 ppm), group III received both K2Cr2O7 and Se (0.5 Na2SeO3 mg/kg of diet), and group IV received Se (0.5 mg/kg of diet) for 3 weeks. Rats exposed to K2Cr2O7 showed an increase of malondialdehyde and protein carbonyl levels and a decrease of sulfhydryl content, glutathione, non-protein
thiol, and vitamin C levels. A decrease of enzyme activities like catalase, glutathione peroxidase, and superoxide dismutase
activities was also noted. Co-administration of Se with K2Cr2O7 restored the parameters cited above to near-normal values. Therefore, our investigation revealed that Se was a useful element
preventing K2Cr2O7-induced erythrocyte damages. 相似文献
85.
The morphology, morphogenesis, and phylogeny of an undescribed oligotrich sensu lato (s. lat.) ciliate, Lynnella semiglobulosa n. g., n. sp., found in Daya Bay, southern China, were investigated. This species shares some features with both oligotrichs sensu stricto and choreotrichs, but most morphological and morphogenetic characters as well as the phylogenetic analysis suggest that it should be assigned into subclass Choreotrichia temporarily. Lynnella semiglobulosa is distinguished from members of all known genera and families of the subclass Choreotrichia by a unique combination of characteristics of the buccal and somatic ciliatures. Thus, a new family Lynnellidae n. fam. and a new genus Lynnella n. g. are proposed for it. The new family is distinguished by an open adoral zone of membranelles (AZM) in which, however, there are no ventral membranelles; the distal and proximal portions of the new adoral zone lie close to each other forming an open circle in stomatogenesis. The new genus Lynnella is characterized by possessing two longitudinally oriented somatic kineties, one dorsal and one ventral, several proximal membranelles progressively lengthened toward the proximal end of adoral zone, and two macronuclear nodules. In phylogenetic analyses based on small subunit rRNA gene sequences, L. semiglobulosa clustered basally to all choreotrichs, but with relatively weak support; nevertheless, the possibility of a relationship with the subclass Oligotrichia was not rejected by the approximately unbiased nor Shimodaira-Hasegawa test. Based on morphological, morphogenetic, and molecular evidence of L. semiglobulosa, it is confirmed that the open AZM should be a plesiomorphic character of oligotrichs s. lat. as suggested previously. 相似文献
86.
87.
Khaled R. Mohamed Amr M. Mohamed Hanan H. Beherei 《Journal of Genetic Engineering and Biotechnology》2011,9(2):111-119
Novel biocomposites were fabricated by impregnating β-tricalcium phosphate (β-TCP)/zirconia particles into the polymers matrix. The composite materials were characterized using thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), Fourier Transform Infrared (FT-IR) analyzes and Scanning Electron Microscopy (SEM). The results confirmed the conversion of hydroxyapatite (HA) to β-TCP at a sintering temperature of 1150 °C with or without zirconia powder. The in vitro behavior was assessed via measurement of calcium and phosphorus ions in SBF (simulated body fluid). FT-IR and SEM of the composites were performed pre and post immersion in SBF. The results prove that the bone like apatite layer formation was enhanced on the β-TCP-Z20/polymeric composite surface more than that on the β-TCP-Z10/polymeric composite. Therefore, the data confirmed that zirconia plays an important role in the enhancement of the apatite formation. The conclusions proved that the β-TCP-Z20/polymeric biocomposites, containing 20% of zirconia, are promising for bone remodeling applications. 相似文献
88.
89.
BackgroundPrivacy legislation in most jurisdictions allows the disclosure of health data for secondary purposes without patient consent if it is de-identified. Some recent articles in the medical, legal, and computer science literature have argued that de-identification methods do not provide sufficient protection because they are easy to reverse. Should this be the case, it would have significant and important implications on how health information is disclosed, including: (a) potentially limiting its availability for secondary purposes such as research, and (b) resulting in more identifiable health information being disclosed. Our objectives in this systematic review were to: (a) characterize known re-identification attacks on health data and contrast that to re-identification attacks on other kinds of data, (b) compute the overall proportion of records that have been correctly re-identified in these attacks, and (c) assess whether these demonstrate weaknesses in current de-identification methods.ConclusionsThe current evidence shows a high re-identification rate but is dominated by small-scale studies on data that was not de-identified according to existing standards. This evidence is insufficient to draw conclusions about the efficacy of de-identification methods. 相似文献
90.
Siddiqui MR Taha A Moorthy K Hussain ME Basir SF Baquer NZ 《Journal of biosciences》2005,30(4):483-490
Trigonella foenum graecum seed powder (TSP) and sodium orthovanadate (SOV) have been reported to have antidiabetic effects. However, SOV exerts hypoglycemic
effects at relatively high doses with several toxic effects. We used low doses of vanadate in combination with TSP and evaluated
their antidiabetic effects on antioxidant enzymes and membrane-linked functions in diabetic rat brains. In rats, diabetes
was induced by alloxan monohydrate (15 mg/100 g body wt.) and they were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP and
a combination of 0.2 mg/ml SOV with 5% TSP for 21 days. Blood glucose levels, activity of superoxide dismutase (SOD), catalase
(CAT), glutathione peroxidase (GPx), Na+/K+ ATPase, membrane lipid peroxidation and fluidity were determined in different fractions of whole brain after 21 days of treatment.
Diabetic rats showed high blood glucose (P < 0.001), decreased activities of SOD, catalase and Na+/K+ ATPase (P < 0.01,P < 0.001 andP < 0.01), increased levels of GPx and MDA (P < 0.01 andP < 0.001) and decreased membrane fluidity (P < 0.01). Treatment with different antidiabetic compounds restored the above-altered parameters. Combined dose ofTrigonella and vanadate was found to be the most effective treatment in normalizing these alterations. Lower doses of vanadate could
be used in combination with TSP to effectively counter diabetic alterations without any toxic effects. 相似文献