全文获取类型
收费全文 | 2924篇 |
免费 | 233篇 |
国内免费 | 1篇 |
专业分类
3158篇 |
出版年
2024年 | 8篇 |
2023年 | 23篇 |
2022年 | 48篇 |
2021年 | 104篇 |
2020年 | 51篇 |
2019年 | 79篇 |
2018年 | 81篇 |
2017年 | 74篇 |
2016年 | 122篇 |
2015年 | 187篇 |
2014年 | 191篇 |
2013年 | 222篇 |
2012年 | 278篇 |
2011年 | 216篇 |
2010年 | 154篇 |
2009年 | 126篇 |
2008年 | 155篇 |
2007年 | 157篇 |
2006年 | 148篇 |
2005年 | 141篇 |
2004年 | 106篇 |
2003年 | 92篇 |
2002年 | 91篇 |
2001年 | 18篇 |
2000年 | 25篇 |
1999年 | 25篇 |
1998年 | 14篇 |
1997年 | 12篇 |
1996年 | 10篇 |
1995年 | 15篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1991年 | 14篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 15篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 16篇 |
1984年 | 10篇 |
1983年 | 9篇 |
1982年 | 11篇 |
1981年 | 4篇 |
1980年 | 10篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1975年 | 4篇 |
1973年 | 6篇 |
1962年 | 4篇 |
排序方式: 共有3158条查询结果,搜索用时 15 毫秒
101.
102.
Varela-Silva MI Dickinson F Wilson H Azcorra H Griffiths PL Bogin B 《Collegium antropologicum》2012,36(1):39-45
This paper focuses on the phenomenon of the nutritional dual-burden in the developing world. Nutritional dual-burden is defined as the coexistence of under-and-over nutrition in the same population/group, the same household/family, or the same person. In this paper we aim: a) to describe the different types of nutritional dual-burden, b) to identify the anthropometric indicators generally used to classify the nutritional dual-burden, c) to focus our attention on a dual-burden group (the Maya from Merida, Yucatan, Mexico), d) to illustrate problems in the categorization of the dual-burden, and e) to suggest possible health implications. Our results show that, for our sample, the prevalence of individual dual-burden among children is very low, but is very high among the mothers and for mother-child pairs (household dual-burden). Most importantly, the criteria used to assess the nutritional status of the individuals and of the families will play an important role in the estimated prevalence of nutritional dual-burden, and this will have practical impacts for health intervention programs. 相似文献
103.
Elisabetta Barresi Chiara Giacomelli Simona Daniele Ilaria Tonazzini Marco Robello Silvia Salerno Ilaria Piano Barbara Cosimelli Giovanni Greco Federico Da Settimo Claudia Martini Maria Letizia Trincavelli Sabrina Taliani 《Bioorganic & medicinal chemistry》2018,26(22):5885-5895
The expression levels and the subcellular localization of adenosine receptors (ARs) are affected in several pathological conditions as a consequence of changes in adenosine release and metabolism. In this respect, labelled probes able to monitor the AR expression could be a useful tool to investigate different pathological conditions. Herein, novel ligands for ARs, bearing the fluorescent 7-nitrobenzofurazan (NBD) group linked to the N1 (1,2) or N10 (3,4) nitrogen of a triazinobenzimidazole scaffold, were synthesized. The compounds were biologically evaluated as fluorescent probes for labelling A1 and A2B AR subtypes in bone marrow-derived mesenchymal stem cells (BM-MSCs) that express both receptor subtypes. The binding affinity of the synthetized compounds towards the different AR subtypes was determined. The probe 3 revealed a higher affinity to A1 and A2B ARs, showing interesting spectroscopic properties, and it was selected as the most suitable candidate to label both AR subtypes in undifferentiated MSCs.Fluorescence confocal microscopy showed that compound 3 significantly labelled ARs on cell membranes and the fluorescence signal was decreased by the cell pre-incubation with the A1 AR and A2B AR selective agonists, R-PIA and BAY 60-6583, respectively, thus confirming the specificity of the obtained signal. In conclusion, compound 3 could represent a useful tool to investigate the expression pattern of both A1 and A2B ARs in different pathological and physiological processes. Furthermore, these results provide an important basis for the design of new and more selective derivatives able to monitor the expression and localization of each different ARs in several tissues and living cells. 相似文献
104.
Sara Garcia‐Serrano Carolina Gutiérrez‐Repiso Montserrat Gonzalo Juan Garcia‐Arnes Sergio Valdes Federico Soriguer Vidal Perez‐Valero Miguel A. Alaminos‐Castillo Juan Francisco Cobos‐Bravo Francisco J. Moreno‐Ruiz Alberto Rodriguez‐Cañete Francisca Rodríguez‐Pacheco Eva Garcia‐Escobar Eduardo García‐Fuentes 《Obesity (Silver Spring, Md.)》2015,23(8):1607-1615
105.
Carmen T. Jacobs Clarke H. Scholtz Federico Escobar Adrian L. V. Davis 《Journal of Insect Conservation》2010,14(4):389-399
There are concerns over the increasing encroachment of humans, domestic livestock, and farming onto Maputo Special Reserve
because of the potential for habitat modification. Therefore, differences between an undisturbed area of the reserve and a
neighbouring farming area are assessed using dung beetle as indicators. In each of the two areas, pig-dung-baited pitfall
traps were used to sample dung beetle assemblages in two contrasting habitats, grassland and forest. Distributional analysis
of the 57 species and 36 942 individuals that were captured, showed that species richness, species turnover, relative abundance
patterns, and biogeographical composition differed strongly between both habitats and areas under different land usage. However,
in analyses that apportion variation, the greatest amounts were related to habitat rather than land usage. Even so, in both
habitats, the total and mean number of species per trap was higher in the farmed area than in the reserve although this was
a significant trend only in grassland. Furthermore, in grassland, widespread species were better represented in the farmed
area than in the reserve whereas in forest, widespread species were poorly represented compared to grassland. Also in forest,
Maputaland endemics were better represented in the reserve than in the farmed area. Further work is necessary to separate
the different geographical, ecological, and land usage factors responsible for the patterns detected in this preliminary study.
Even so, there are clearly differences between the Maputo Special Reserve and the farmed area. 相似文献
106.
Ishizuka T Hess RA Reuter B Federico MS Yamada Y 《Journal of strength and conditioning research / National Strength & Conditioning Association》2011,25(7):1905-1910
Health and fitness professionals working with athletes could establish effective and safe practice and training programs if recovery time on dynamic balance from exertion was available. Research investigating the time needed to recover dynamic limits of stability (LOS) from exertion has not been reported. The purpose of this study was to determine the recovery timeline on LOS from functional fatigue in collegiate athletes. Eighteen athletes (11 men, 7 women) from Division II collegiate soccer team who passed prescreening tests to identify their fitness levels were randomly tested on 2 different days by condition (fatigue or nonfatigue). Functional fatigue was determined by using the Borg 15-point rating of perceived exertion (RPE) scale. Subjects were tested on LOS on the Biodex Balance System pre, post, 10, 15, and 20 minutes for each condition. The main effect for condition was not significant (F() = 0.004, p = 0.948), whereas the main effect for time was significant (F(4,64) = 6.167, p < 0.001). The RPE scoring revealed the significant main effect in FATIGUE (F(2.69, 45.73) = 234.8, p < 0.001). In conclusion, 20 minutes of functional activity will likely have a negative influence on dynamic balance, with balance recovery occurring within 10 minutes after the cessation of exercise in Division II collegiate soccer athletes. Moreover, the level of exertion measured by RPE would correspond to athletes' ability to control their center of mass. 相似文献
107.
Anna M. Mileo Claudia Abbruzzese Stefano Mattarocci Emanuele Bellacchio Paola Pisano Antonio Federico Vittoria Maresca Mauro Picardo Alessandra Giorgi Bruno Maras M. Eugenia Schininà Marco G. Paggi 《PloS one》2009,4(10)
Background
Human Papillomavirus (HPV)-16 is a paradigm for “high-risk” HPVs, the causative agents of virtually all cervical carcinomas. HPV E6 and E7 viral genes are usually expressed in these tumors, suggesting key roles for their gene products, the E6 and E7 oncoproteins, in inducing malignant transformation.Methodology/Principal Findings
By protein-protein interaction analysis, using mass spectrometry, we identified glutathione S-transferase P1-1 (GSTP1) as a novel cellular partner of the HPV-16 E7 oncoprotein. Following mapping of the region in the HPV-16 E7 sequence that is involved in the interaction, we generated a three-dimensional molecular model of the complex between HPV-16 E7 and GSTP1, and used this to engineer a mutant molecule of HPV-16 E7 with strongly reduced affinity for GSTP1.When expressed in HaCaT human keratinocytes, HPV-16 E7 modified the equilibrium between the oxidized and reduced forms of GSTP1, thereby inhibiting JNK phosphorylation and its ability to induce apoptosis. Using GSTP1-deficient MCF-7 cancer cells and siRNA interference targeting GSTP1 in HaCaT keratinocytes expressing either wild-type or mutant HPV-16 E7, we uncovered a pivotal role for GSTP1 in the pro-survival program elicited by its binding with HPV-16 E7.Conclusions/Significance
This study provides further evidence of the transforming abilities of this oncoprotein, setting the groundwork for devising unique molecular tools that can both interfere with the interaction between HPV-16 E7 and GSTP1 and minimize the survival of HPV-16 E7-expressing cancer cells. 相似文献108.
Legumes can acquire nitrogen through a symbiotic interaction with rhizobial bacteria. The initiation of this process is determined by a molecular dialogue between the two partners. Legume roots exude flavonoids that induce the expression of the bacterial nodulation genes, which encode proteins involved in the synthesis and secretion of signals called Nod factors (NFs). NFs signal back to the plant root and trigger several responses, leading to bacterial invasion and nodule formation. Here, we describe the molecular and cellular characterization of a Phaseolus vulgaris non-nodulating mutant (NN-mutant). Root hair cells of the NN-mutant plant respond with swelling and branching when inoculated with Rhizobium etli, albeit without curling induction. Furthermore, neither initiation of cell division in the outer cortex, nor entrapment of bacteria nor infection thread formation was observed. Both the bean wild-type and the NN-mutant responded with elevated intracellular calcium changes in the root hairs. Although the NN-mutant is deficient in early nodulin gene expression when inoculated with R. etli, it can be effectively colonized by arbuscular mycorrhizal fungi (Glomus intraradices). Our data indicate that the P. vulgaris NN-mutant is not blocked at the NFs early perception stage, but at later downstream stages between Ca2+ signaling and early nodulin induction. This supports the idea that both microsymbionts are perceived and trigger different downstream pathways in the host plant. 相似文献
109.
Federico Fischer Debora Raimondi Alessandro Aliverti Giuliana Zanetti 《European journal of biochemistry》2002,269(12):3005-3013
The gene fprA of Mycobacterium tuberculosis, encoding a putative protein with 40% identity to mammalian adrenodoxin reductase, was expressed in Escherichia coli and the protein purified to homogeneity. The 50-kDa protein monomer contained one tightly bound FAD, whose fluorescence was fully quenched. FprA showed a low ferric reductase activity, whereas it was very active as a NAD(P)H diaphorase with dyes. Kinetic parameters were determined and the specificity constant (kcat/Km) for NADPH was two orders of magnitude larger than that of NADH. Enzyme full reduction, under anaerobiosis, could be achieved with a stoichiometric amount of either dithionite or NADH, but not with even large excess of NADPH. In enzyme titration with substoichiometric amounts of NADPH, only charge transfer species (FAD-NADPH and FADH2-NADP+) were formed. At NADPH/FAD ratios higher than one, the neutral FAD semiquinone accumulated, implying that the semiquinone was stabilized by NADPH binding. Stabilization of the one-electron reduced form of the enzyme may be instrumental for the physiological role of this mycobacterial flavoprotein. By several approaches, FprA was shown to be able to interact productively with [2Fe-2S] iron-sulfur proteins, either adrenodoxin or plant ferredoxin. More interestingly, kinetic parameters of the cytochrome c reductase reaction catalyzed by FprA in the presence of a 7Fe ferredoxin purified from M. smegmatis were determined. A Km value of 30 nm and a specificity constant of 110 microM(-1) x s(-1) (10 times greater than that for the 2Fe ferredoxin) were determined for this ferredoxin. The systematic name for FprA is therefore NADPH-ferredoxin oxidoreductase. 相似文献
110.
Fragmentation of contaminant and endogenous DNA in ancient samples determined by shotgun sequencing; prospects for human palaeogenomics 总被引:1,自引:0,他引:1
García-Garcerà M Gigli E Sanchez-Quinto F Ramirez O Calafell F Civit S Lalueza-Fox C 《PloS one》2011,6(8):e24161
BACKGROUND: Despite the successful retrieval of genomes from past remains, the prospects for human palaeogenomics remain unclear because of the difficulty of distinguishing contaminant from endogenous DNA sequences. Previous sequence data generated on high-throughput sequencing platforms indicate that fragmentation of ancient DNA sequences is a characteristic trait primarily arising due to depurination processes that create abasic sites leading to DNA breaks. METHODOLOGY/PRINCIPALS FINDINGS: To investigate whether this pattern is present in ancient remains from a temperate environment, we have 454-FLX pyrosequenced different samples dated between 5,500 and 49,000 years ago: a bone from an extinct goat (Myotragus balearicus) that was treated with a depurinating agent (bleach), an Iberian lynx bone not subjected to any treatment, a human Neolithic sample from Barcelona (Spain), and a Neandertal sample from the El Sidrón site (Asturias, Spain). The efficiency of retrieval of endogenous sequences is below 1% in all cases. We have used the non-human samples to identify human sequences (0.35 and 1.4%, respectively), that we positively know are contaminants. CONCLUSIONS: We observed that bleach treatment appears to create a depurination-associated fragmentation pattern in resulting contaminant sequences that is indistinguishable from previously described endogenous sequences. Furthermore, the nucleotide composition pattern observed in 5' and 3' ends of contaminant sequences is much more complex than the flat pattern previously described in some Neandertal contaminants. Although much research on samples with known contaminant histories is needed, our results suggest that endogenous and contaminant sequences cannot be distinguished by the fragmentation pattern alone. 相似文献