全文获取类型
收费全文 | 6286篇 |
免费 | 443篇 |
国内免费 | 288篇 |
出版年
2024年 | 8篇 |
2023年 | 70篇 |
2022年 | 160篇 |
2021年 | 159篇 |
2020年 | 160篇 |
2019年 | 198篇 |
2018年 | 204篇 |
2017年 | 137篇 |
2016年 | 177篇 |
2015年 | 218篇 |
2014年 | 318篇 |
2013年 | 435篇 |
2012年 | 207篇 |
2011年 | 427篇 |
2010年 | 336篇 |
2009年 | 332篇 |
2008年 | 312篇 |
2007年 | 345篇 |
2006年 | 326篇 |
2005年 | 364篇 |
2004年 | 273篇 |
2003年 | 208篇 |
2002年 | 178篇 |
2001年 | 78篇 |
2000年 | 71篇 |
1999年 | 76篇 |
1998年 | 93篇 |
1997年 | 83篇 |
1996年 | 60篇 |
1995年 | 59篇 |
1994年 | 62篇 |
1993年 | 59篇 |
1992年 | 60篇 |
1991年 | 33篇 |
1990年 | 34篇 |
1989年 | 37篇 |
1988年 | 20篇 |
1987年 | 17篇 |
1986年 | 19篇 |
1985年 | 64篇 |
1984年 | 151篇 |
1983年 | 96篇 |
1982年 | 101篇 |
1981年 | 57篇 |
1980年 | 47篇 |
1979年 | 34篇 |
1978年 | 22篇 |
1977年 | 8篇 |
1975年 | 10篇 |
1974年 | 7篇 |
排序方式: 共有7017条查询结果,搜索用时 15 毫秒
891.
892.
Tissue oximetry by diffusive reflective visible light spectroscopy: Comparison of algorithms and their robustness
下载免费PDF全文
![点击此处可从《Journal of biophotonics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
It is essential to measure tissue oxygen saturation (StO2) locally and in thin layers of tissue, for example, the bronchial mucosa, skin flaps and small bones. Visible light spectroscopy (VLS) with a shallow penetration depth is suitable method. Although several VLS algorithms have been developed and described, they have not yet been compared to each other. This hinders attempts to compare the clinical results obtained by different algorithms. To address this issue, we compared the algorithms of Harrison, Knoefel, Pittman‐Duling, Sato and our OxyVLS oximeter, which applies the algorithm from Wodick and Lübbers, in a liquid phantom with optical properties of human tissue. We generally observed considerable differences between the algorithms, which were StO2 dependent. Exceptions were OxyVLS and Sato, showing a high level of agreement with negligible StO2 dependency. In spite of the considerable deviation between the other algorithms, the difference of StO2 between them in clinically normal StO2 was <10%. We did not observe any dependency of the algorithms on hemoglobin content of the phantom or temperature. 相似文献
893.
Comments on recent reports on infrared spectral detection of disease markers in blood components
下载免费PDF全文
![点击此处可从《Journal of biophotonics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Max Diem 《Journal of biophotonics》2018,11(7)
The search for disease markers in whole blood, or easily accessible blood components by spectral methods is a highly important aspect in the field of biophotonic research for disease diagnostics and screening, since it promises a minimally invasive approach to assess an individual's state of health. Fourier transform infrared spectroscopy, in particular, promises to be a fast, inexpensive method to search for markers of disease, since it detects variation in the proteome, lipidome and metabolome of biofluids, or activation of immune cells. However, the analysis of any materials by spectral methods is confounded by external factors such as those related to sample deposition and data acquisition, and by inherent variations in blood plasma concentration of small molecules (lactate, carbonate, phosphate, glucose) that varies between individual subjects and even for a given individual, as a function of time. Furthermore, observed differences in spectral patterns between patient samples and the control group may be due to the body's immune response (in particular, to the albumin to globulin ratio) and therefore, may not be specific to disease. These factors need to be accounted for in any effort to reliably detect much smaller variations in the concentration of disease‐specific markers. 相似文献
894.
Himadri Biswas 《Journal of biomolecular structure & dynamics》2018,36(8):2179-2193
The major tuber storage protein of Colocasia esculenta, is a monocot mannose-binding, widely used dietary lectin, containing two polypeptides of 12.0 and 12.4 kDa. By both gel filtration and dynamic light scattering at pH 7.2, the lectin has a α2β2 form of apparent molecular mass of 48.2 kDa and a hydrodynamic radius of 6.1 ± .2 nm; however, at pH 3, it migrates as αβ and has a reduced hydrodynamic radius of 4.6 ± .3 nm. Our circular dichroism spectroscopy studies show that the lectin retains approximately 100% of its secondary structure between pH 2–8, going down to ~90% for extreme acidic/alkaline conditions. The fluorescence emission maxima of 346 to 350 nm for pH 4 to 10 show that the tryptophan residues are relatively exposed. The unfolding is a simple two-state process, N4 ? 4U, as seen in our denaturation scan profiles. These denaturation profiles, monitored separately by fluorescence, far-UV CD, and near-UV CD, are completely super imposable. Analyses of these profiles provide an estimate of several thermodynamic parameters at each guanidinium chloride concentration, including the melting temperature Tg, which is 346.9 K in 0 M, but lowers to 321.8 K in 3.6 M. Dimeric and tetrameric interfaces observed in the crystal structure for the same protein are used to rationalize solution data in some detail. 相似文献
895.
Mohammed A. Khedr Melendhran Pillay Sandeep Chandrashekharappa Deepak Chopra Bandar E. Aldhubiab Mahesh Attimarad 《Journal of biomolecular structure & dynamics》2018,36(8):2163-2178
A series of trisubstituted indolizine analogues has been designed as a result of a fragment-based approach to target the inhibition of mycobacterial enoyl-acyl carrier protein reductase. Anti-tuberculosis (TB) screening of the characterized compounds by a resazurin microplate assay method revealed that ethyl group at second position of indolizine nucleus exhibited activity against susceptible and multidrug-resistant strains of Mycobacterium tuberculosis at concentration of 5.5 and 11.3 μg/mL, respectively. A molecular docking study was also conducted to evaluate the stability of the active compounds, and compound with ethyl substitution at second position of indolizine nucleus showed the highest free binding energy of ΔG ?24.11 (kcal/mol), a low clash score of 3.04, and high lipo score of ?13.33. Indolizine analog with ethyl substitution at second position demonstrated Molecular Mechanics/Generalized Born Surface Area (?23.85 kcal/mol). Two molecular dynamics studies were computed (100 ps and 50 ns) to calculate the relationship between the potential and kinetic energies of the active anti-TB compound with time and temperature. The discovery of this lead may have a positive impact on anti-TB drug discovery. 相似文献
896.
Verena Hiebl Angela Ladurner Simone Latkolik Verena M. Dirsch 《Biotechnology advances》2018,36(6):1657-1698
Nuclear receptors (NRs) represent attractive targets for the treatment of metabolic syndrome-related diseases. In addition, natural products are an interesting pool of potential ligands since they have been refined under evolutionary pressure to interact with proteins or other biological targets.This review aims to briefly summarize current basic knowledge regarding the liver X (LXR) and farnesoid X receptors (FXR) that form permissive heterodimers with retinoid X receptors (RXR). Natural product-based ligands for these receptors are summarized and the potential of LXR, FXR and RXR as targets in precision medicine is discussed. 相似文献
897.
Giorgia Letizia Marcone Elisa Binda Francesca Berini Flavia Marinelli 《Biotechnology advances》2018,36(2):534-554
Glycopeptide antibiotics are drugs of last resort for treating severe infections caused by multi-drug resistant Gram-positive pathogens. First-generation glycopeptides (vancomycin and teicoplanin) are produced by soil-dwelling actinomycetes. Second-generation glycopeptides (dalbavancin, oritavancin, and telavancin) are semi-synthetic derivatives of the progenitor natural products. Herein, we cover past and present biotechnological approaches for searching for and producing old and new glycopeptide antibiotics. We review the strategies adopted to increase microbial production (from classical strain improvement to rational genetic engineering), and the recent progress in genome mining, chemoenzymatic derivatization, and combinatorial biosynthesis for expanding glycopeptide chemical diversity and tackling the never-ceasing evolution of antibiotic resistance. 相似文献
898.
Irena Trbojević-Akmačić Frano Vučković Marija Vilaj Andrea Skelin Lennart C. Karssen Jasminka Krištić Julija Jurić Ana Momčilović Jelena Šimunović Massimo Mangino Manuela De Gregori Maurizio Marchesini Concetta Dagostino Jerko Štambuk Mislav Novokmet Richard Rauck Yurii S. Aulchenko Dragan Primorac Gordan Lauc 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2124-2133
Background
Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.Methods
Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery.Results
We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients' plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP.Conclusions
Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation.General significance
To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology. 相似文献899.
Pedro Jimenez‐Sandoval Ezequiel A. Madrigal‐Carrillo Hugo A. Santamaría‐Suárez Daniel Maturana Itzel Rentería‐González Claudia G. Benitez‐Cardoza Alfredo Torres‐Larios Luis G. Brieba 《Proteins》2018,86(7):802-812
Antibodies recognize protein targets with great affinity and specificity. However, posttranslational modifications and the presence of intrinsic disulfide‐bonds pose difficulties for their industrial use. The immunoglobulin fold is one of the most ubiquitous folds in nature and it is found in many proteins besides antibodies. An example of a protein family with an immunoglobulin‐like fold is the Cysteine Protease Inhibitors (ICP) family I42 of the MEROPs database for protease and protease inhibitors. Members of this protein family are thermostable and do not present internal disulfide bonds. Crystal structures of several ICPs indicate that they resemble the Ig‐like domain of the human T cell co‐receptor CD8α As ICPs present 2 flexible recognition loops that vary accordingly to their targeted protease, we hypothesize that members of this protein family would be ideal to design peptide aptamers that mimic protein‐protein interactions. Herein, we use an ICP variant from Entamoeba histolytica (EhICP1) to mimic the interaction between p53 and MDM2. We found that a 13 amino‐acid peptide derived from p53 can be introduced in 2 variable loops (DE, FG) but not the third (BC). Chimeric EhICP1‐p53 form a stable complex with MDM2 at a micromolar range. Crystal structure of the EhICP1‐p53(FG)‐loop variant in complex with MDM2 reveals a swapping subdomain between 2 chimeric molecules, however, the p53 peptide interacts with MDM2 as in previous crystal structures. The structural details of the EhICP1‐p53(FG) interaction with MDM2 resemble the interaction between an antibody and MDM2. 相似文献
900.