全文获取类型
收费全文 | 3957篇 |
免费 | 292篇 |
国内免费 | 1篇 |
专业分类
4250篇 |
出版年
2023年 | 10篇 |
2022年 | 35篇 |
2021年 | 65篇 |
2020年 | 39篇 |
2019年 | 50篇 |
2018年 | 83篇 |
2017年 | 60篇 |
2016年 | 120篇 |
2015年 | 209篇 |
2014年 | 218篇 |
2013年 | 283篇 |
2012年 | 375篇 |
2011年 | 368篇 |
2010年 | 186篇 |
2009年 | 164篇 |
2008年 | 262篇 |
2007年 | 269篇 |
2006年 | 224篇 |
2005年 | 238篇 |
2004年 | 201篇 |
2003年 | 181篇 |
2002年 | 181篇 |
2001年 | 32篇 |
2000年 | 24篇 |
1999年 | 39篇 |
1998年 | 40篇 |
1997年 | 45篇 |
1996年 | 37篇 |
1995年 | 24篇 |
1994年 | 25篇 |
1993年 | 18篇 |
1992年 | 19篇 |
1991年 | 17篇 |
1990年 | 14篇 |
1989年 | 11篇 |
1988年 | 12篇 |
1987年 | 10篇 |
1986年 | 17篇 |
1985年 | 7篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1978年 | 4篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有4250条查询结果,搜索用时 0 毫秒
51.
Annelies Bronckaers Petra Hilkens Yanick Fanton Tom Struys Pascal Gervois Constantinus Politis Wendy Martens Ivo Lambrichts 《PloS one》2013,8(8)
Angiogenesis, the formation of capillaries from pre-existing blood vessels, is a key process in tissue engineering. If blood supply cannot be established rapidly, there is insufficient oxygen and nutrient transport and necrosis of the implanted tissue will occur. Recent studies indicate that the human dental pulp contains precursor cells, named dental pulp stem cells (hDPSC) that show self-renewal and multilineage differentiation capacity. Since these cells can be easily isolated, cultured and cryopreserved, they represent an attractive stem cell source for tissue engineering. Until now, only little is known about the angiogenic abilities and mechanisms of the hDPSC. In this study, the angiogenic profile of both cell lysates and conditioned medium of hDPSC was determined by means of an antibody array. Numerous pro-and anti-angiogenic factors such as vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and endostatin were found both at the mRNA and protein level. hDPSC had no influence on the proliferation of the human microvascular endothelial cells (HMEC-1), but were able to significantly induce HMEC-1 migration in vitro. Addition of the PI3K-inhibitor and the MEK-inhibitor U0126 to the HMEC-1 inhibited this effect, suggesting that both Akt and ERK pathways are involved in hDPSC-mediated HMEC-1 migration. Antibodies against VEGF also abolished the chemotactic actions of hDPSC. Furthermore, in the chicken chorioallantoic membrane (CAM) assay, hDPSC were able to significantly induce blood vessel formation. In conclusion, hDPSC have the ability to induce angiogenesis, meaning that this stem cell population has a great clinical potential, not only for tissue engineering but also for the treatment of chronic wounds, stroke and myocardial infarctions. LY294002相似文献
52.
Shinichi Sunagawa Jens Roat Kultima Paul I Costea Aurélien Amiot Jürgen Böhm Francesco Brunetti Nina Habermann Rajna Hercog Moritz Koch Alain Luciani Daniel R Mende Martin A Schneider Petra Schrotz‐King Christophe Tournigand Jeanne Tran Van Nhieu Takuji Yamada Jürgen Zimmermann Vladimir Benes Matthias Kloor Cornelia M Ulrich Magnus von Knebel Doeberitz Iradj Sobhani Peer Bork 《Molecular systems biology》2014,10(11)
Several bacterial species have been implicated in the development of colorectal carcinoma (CRC),
but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be
explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that
distinguished CRC patients from tumor-free controls in a study population of 156 participants.
Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and
when both approaches were combined, sensitivity improved > 45% relative to the FOBT,
while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ
significantly between early- and late-stage cancer and could be validated in independent patient and
control populations (N = 335) from different countries. CRC-associated
changes in the fecal microbiome at least partially reflected microbial community composition at the
tumor itself, indicating that observed gene pool differences may reveal tumor-related
host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in
controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an
increase of lipopolysaccharide metabolism. 相似文献
53.
Jin Young K. Kininmonth Stuart Lundgren Petra B. van Oppen Madeleine J. H. Willis Bette L. 《Coral reefs (Online)》2020,39(1):147-158
Coral Reefs - In the face of unprecedented rates of environmental alterations, the necessity to predict the capacity of corals to respond adaptively in a complex ecological system is becoming... 相似文献
54.
55.
Petra Griekspoor Frances M. Colles Noel D. McCarthy Philip M. Hansbro Chris Ashhurst‐Smith Björn Olsen Dennis Hasselquist Martin C. J. Maiden Jonas Waldenström 《Molecular ecology》2013,22(5):1463-1472
Zoonotic pathogens often infect several animal species, and gene flow among populations infecting different host species may affect the biological traits of the pathogen including host specificity, transmissibility and virulence. The bacterium Campylobacter jejuni is a widespread zoonotic multihost pathogen, which frequently causes gastroenteritis in humans. Poultry products are important transmission vehicles to humans, but the bacterium is common in other domestic and wild animals, particularly birds, which are a potential infection source. Population genetic studies of C. jejuni have mainly investigated isolates from humans and domestic animals, so to assess C. jejuni population structure more broadly and investigate host adaptation, 928 wild bird isolates from Europe and Australia were genotyped by multilocus sequencing and compared to the genotypes recovered from 1366 domestic animal and human isolates. Campylobacter jejuni populations from different wild bird species were distinct from each other and from those from domestic animals and humans, and the host species of wild bird was the major determinant of C. jejuni genotype, while geographic origin was of little importance. By comparison, C. jejuni differentiation was restricted between more phylogenetically diverse farm animals, indicating that domesticated animals may represent a novel niche for C. jejuni and thereby driving the evolution of those bacteria as they exploit this niche. Human disease is dominated by isolates from this novel domesticated animal niche. 相似文献
56.
Shedding light on host niches: label‐free in situ detection of Mycobacterium gordonae via carotenoids in macrophages by Raman microspectroscopy 下载免费PDF全文
Anja Silge Elias Abdou Kilian Schneider Susann Meisel Thomas Bocklitz Hui‐Wen Lu‐Walther Rainer Heintzmann Petra Rösch Jürgen Popp 《Cellular microbiology》2015,17(6):832-842
Macrophages are the primary habitat of pathogenic mycobacteria during infections. Current research about the host–pathogen interaction on the cellular level is still going on. The present study proves the potential of Raman microspectroscopy as a label‐free and non‐invasive method to investigate intracellular mycobacteria in situ. Therefore, macrophages were infected with Mycobacterium gordonae, a mycobacterium known to cause inflammation linked to intracellular survival in macrophages. Here, we show that Raman maps provided spatial and spectral information about the position of bacteria within determined cell margins of macrophages in two‐dimensional scans and in three‐dimensional image stacks. Simultaneously, the relative intracellular concentration and distributions of cellular constituents such as DNA, proteins and lipids provided phenotypic information about the infected macrophages. Locations of bacteria outside or close to the outer membrane of the macrophages were notably different in their spectral pattern compared with intracellular once. Furthermore, accumulations of bacteria inside of macrophages exhibit distinct spectral/molecular information because of the chemical composition of the intracellular microenvironment. The data show that the connection of microscopically and chemically gained information provided by Raman microspectroscopy offers a new analytical way to detect and to characterize the mycobacterial infection of macrophages. 相似文献
57.
Elgar Susanne Quabius Silke Tribius Alessa Heinrichs Dirk Haaser Andr Kühnel Martin Laudien Florian Hoppe Robert Mlynski Petra Ambrosch Markus Hoffmann 《Translational oncology》2021,14(2)
Previous studies describe a correlation between HPV-positivity and non-smoking in TSCC; p16INK4A-expression as surrogate-marker for HPV-DNA/RNA-positivity is discussed controversially. In the present study, these parameters are assessed prospectively. HPV-status of sputum and tonsillar-swabs was analyzed to determine their validity as surrogate-marker for tissue-HPV-status.TSCC- (n = 52) and non-neoplastic tonsillar tissue (n = 163) were analyzed. HPV-DNA- and HPV-RNA-status of total sputum, cellular fraction and supernatants, tonsillar-swabs and -tissue was determined by (RT)-PCR. Immunohistochemistry determined p16INK4A-expression.23/163 (14.2%) non-neoplastic tonsils were HPV-DNA-positive; five patients (3 HPV16, 2 HPV11) had active HPV-infections (HPV-RNA-positive), in all biomaterials. 140/163 (85.9%) patients were either HPV-DNA-positive or HPV-DNA-negative in all samples. 21/52 (40.4%) TSCC-tonsils were HPV-DNA-positive; 17 patients were HPV-RNA-positive (14 HPV16; 4 HPV18). 40/52 (76.9%) TSCC-patients were congruent in all biomaterials. p16INK4A-expression alone would have misclassified the HPV-status of 14/52 (26.2%) TSCC-patients.This prospective study confirms the discrepancy between HPV-status and p16INK4A-expression and the significant correlation between non-smoking and HPV-DNA-positivity. HPV-sputum- and/or swab-results do not consistently match tissue-results, possibly having (detrimental) consequences if those were used to assess tissue-HPV-status. In the 5 patients with active HPV infection in the non-neoplasitic tonsils, tonsillectomy likely prevented subsequent development of TSCC. 相似文献
58.
Jürgen Voigt Dieter Mergenhagen Petra Münzner Hans-Peter Vogeler Klaus Nagel 《Planta》1989,178(4):456-462
In light-dark-synchronized cultures of the unicellular green algaChlamydomonas reinhardtii, release of zoospores from the wall of the mother cell normally takes place during the second half of the dark period. The recently isolated mutant ls, however, needs light for the liberation of zoospores when grown photoautotrophically under a 12 h light-12 h dark regime. The light-induced release of zoospores was found to be prevented by addition of the photosystem-II inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Furthermore, light dependence of this process was shown to be abolished when the mutant ls was grown either photoautotrophically under a 14 h light-10 h dark regime or in the presence of acetate. Our findings indicate that the light-dependency of zoospore liberation observed in cultures of this particular mutant during photoautotrophic growth under a 12 h light-12 h dark regime might be attributed to an altered energy metabolism. The light-induced release of zoospores was found to be prevented by addition of cycloheximide or chloramphenicol, antibiotics which inhibit protein biosynthesis by cytoplasmic and organellar ribosomes, respectively. Actinomycin D, an inhibitor of RNA synthesis, however, did not affect the light-induced liberation of zoospores.Sporangia accumulate in stationary cultures of the mutant ls. Release of zoospores was observed when these sporangia were collected by centrifugation and incubated in the light after resuspension in fresh culture medium. Since liberation of zoospores was not observed after dilution of the stationary cultures with fresh culture medium, we suppose that components which interfere with the action of the sporangial autolysin are accumulated in the culture medium of the mutant ls.Abbreviation DCMU
3-(3,4-dichlorophenyl)-1,1-dimethylurea 相似文献
59.
Stressful events may contribute to low reproductive efficiency due to glucocorticoid-mediated inhibition of hormone secretion in a variety of species. We therefore investigated effects of stress related to management of mares around artificial insemination on secretion of cortisol and fertility parameters. To avoid further disturbance of mares by frequent blood sampling, faecal cortisol metabolites (fCM) were determined instead (sample collection at 8-h intervals). A total of 50 mares (16 maiden, 17 barren, 12 foaling, 5 teaching mares) were included in the study. Mares were brought to the AI centre in vans or trailers (driving time between 30 min and 5 h). Teaching mares were housed in the clinic and had therefore not to be transported. Mares were inseminated either with fresh/cooled-shipped or frozen semen. Rectal palpations and ultrasound examinations were performed at 24- to 48-h intervals, in animals inseminated with frozen semen at 6-h intervals during the last 48 h before ovulation. In maiden, barren and foaling mares, fCM concentrations in faeces tended to be higher than in teaching mares at all times after arrival at the AI centre. At 24 and 48 h after arrival, fCM concentrations in maiden mares were significantly higher than in teaching mares (24h: maiden mares 12.3+/-3.1 ng/g, barren mares 8.5+/-1.2 ng/g, foaling mares 11.0+/-2.4 ng/g, teaching mares 3.8+/-0.6 ng/g, p<0.05). The time from arrival at the AI centre to detection of ovulation did not differ among the different groups of mares and was 4.5+/-0.4, 5.0+/-0.5, 3.8+/-0.5 and 5.6+/-0.9 days in maiden, barren, foaling and teaching mares, respectively (n.s.). Pregnancy rates were 53, 53, 55 and 60%, respectively (n.s.). The time from arrival at the AI centre to detection of ovulation was 4.4+/-0.3 days and 4.9+/-0.3 days in mares inseminated with fresh/shipped (n=39) or frozen semen (n=11; n.s.), respectively. The frequency of follicular checks influenced fCM secretion and was statistically significant at 16 h before ovulation (fresh/shipped semen: fCM 6.9+/-0.7 ng/g faeces, frozen semen: fCM 16.9+/-5.2 ng/g faeces, p<0.01). In the mare, gynaecological examinations seem to act as stressors and may increase cortisol secretion. However, this does not negatively influence fertility and in animals familiar with that procedure fCM concentrations are not elevated. 相似文献
60.
Bax is a critical regulator of physiological cell death that increases the permeability of the outer mitochondrial membrane and facilitates the release of the so-called apoptotic factors during apoptosis. The molecular mechanism of action is unknown, but it probably involves the formation of partially lipidic pores induced by Bax. To investigate the interaction of Bax with lipid membranes and the physical changes underlying the formation of Bax pores, we used an active peptide derived from helix 5 of this protein (Bax-alpha5) that is able to induce Bax-like pores in lipid bilayers. We report the decrease of line tension due to peptide binding both at the domain interface in phase-separated lipid bilayers and at the pore edge in atomic force microscopy film-rupture experiments. Such a decrease in line tension may be a general strategy of pore-forming peptides and proteins, as it affects the energetics of the pore and stabilizes the open state. 相似文献