全文获取类型
收费全文 | 2385篇 |
免费 | 219篇 |
出版年
2023年 | 17篇 |
2022年 | 30篇 |
2021年 | 49篇 |
2020年 | 40篇 |
2019年 | 58篇 |
2018年 | 79篇 |
2017年 | 62篇 |
2016年 | 99篇 |
2015年 | 130篇 |
2014年 | 141篇 |
2013年 | 154篇 |
2012年 | 218篇 |
2011年 | 195篇 |
2010年 | 138篇 |
2009年 | 103篇 |
2008年 | 131篇 |
2007年 | 108篇 |
2006年 | 109篇 |
2005年 | 80篇 |
2004年 | 92篇 |
2003年 | 91篇 |
2002年 | 81篇 |
2001年 | 34篇 |
2000年 | 33篇 |
1999年 | 26篇 |
1998年 | 13篇 |
1997年 | 16篇 |
1996年 | 16篇 |
1995年 | 14篇 |
1994年 | 16篇 |
1993年 | 16篇 |
1992年 | 13篇 |
1991年 | 15篇 |
1990年 | 13篇 |
1989年 | 18篇 |
1988年 | 18篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1984年 | 7篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 9篇 |
1975年 | 8篇 |
1974年 | 10篇 |
1973年 | 9篇 |
1972年 | 5篇 |
1968年 | 5篇 |
1966年 | 6篇 |
排序方式: 共有2604条查询结果,搜索用时 585 毫秒
161.
The regulation exerted by ammonium and other nitrogen sources on amino acid utilization was studied in swollen spores of Penicillium chrysogenum. Ammonium prevented the L-lysine, L-arginine and L-ornithine utilization by P. chrysogenum swollen spores seeded in complete media, but not in carbon-deficient media. Transport of L-[14C]lysine into spores incubated in presence of carbon and nitrogen sources was fully inhibited by ammonium ions (35 mM). However, in carbon-derepressed conditions (growth in absence of sugars, with amino acids as the sole carbon source) L-[14C]lysine transport was only partially inhibited. Competition experiments showed that L-lysine (1 mM) inhibits the utilization of L-arginine, and vice versa, L-arginine inhibits the L-lysine uptake. High concentrations of L-ornithine (100 mM) prevented the L-lysine and L-arginine utilization in P. chrysogenum swollen spores. In summary, ammonium seems to prevent the utilization of basic amino acids in P. chrysogenum spores by inhibiting the transport of these amino acids through their specific transport system(s), but not through the general amino acid transport system that is operative under carbon-derepression conditions. 相似文献
162.
Detection of intracytoplasmic cytokines by flow cytometry 总被引:1,自引:0,他引:1
Santiago MA Luca PM Bertho AL Azeredo-Coutinho RB Coutinho SG 《Memórias do Instituto Oswaldo Cruz》2000,95(3):401-402
Flow cytometry has been used as a powerful technique for studying cell surface antigen expression as well as intracellular molecules. Its capability of analyzing multiple parameters simultaneously on a single cell has allowed identification and studies of functional cell subsets within heterogeneous populations. In this respect, several techniques have been developed during the past few years to study cytokine-producing cells by flow cytometry in humans and several animal models. 相似文献
163.
Loss of G(1)/S checkpoint in human immunodeficiency virus type 1-infected cells is associated with a lack of cyclin-dependent kinase inhibitor p21/Waf1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Clark E Santiago F Deng L Chong S de La Fuente C Wang L Fu P Stein D Denny T Lanka V Mozafari F Okamoto T Kashanchi F 《Journal of virology》2000,74(11):5040-5052
164.
Overexpression of p21(waf1) in human T-cell lymphotropic virus type 1-infected cells and its association with cyclin A/cdk2 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
de La Fuente C Santiago F Chong SY Deng L Mayhood T Fu P Stein D Denny T Coffman F Azimi N Mahieux R Kashanchi F 《Journal of virology》2000,74(16):7270-7283
165.
The early stages of the Panulirus echinatus were hatched and reared in the laboratory. Ovigerous females were captured in their habitat and carefully transported to the laboratory. Larvae were transferred in a recirculation water tank at a density of 10 larvae.L(-1). The larvae were fed on Artemia and gonads of mussel Brachydonts sp. Microalgae Dunaliella viridis was added at a concentration of 150 x 10(4) cell.mL(-1). Larvae and exuviae of each zoeal stage were preserved in an alcohol 70% + glycerin (1:1) solution. The phyllosomas moulted eight times; the intermoulting period of each instar averaged about 7 to 10 days. The main morphological changes of each appendage were described in detail, illustrated and compared with previous reports. 相似文献
166.
Cendrine Faivre‐Moskalenko Mélanie Koelblen Fabien Montel Santiago Cuesta‐Lopez Olivier Bornet Françoise Guerlesquin Thomas Godet Julien Moukhtar Françoise Argoul Anne‐Cécile Déclais David M J Lilley Stephen C Y Ip Stephen C West Eric Gilson Marie‐Josèphe Giraud‐Panis 《The EMBO journal》2009,28(6):641-651
The ability of the telomeric DNA‐binding protein, TRF2, to stimulate t‐loop formation while preventing t‐loop deletion is believed to be crucial to maintain telomere integrity in mammals. However, little is known on the molecular mechanisms behind these properties of TRF2. In this report, we show that TRF2 greatly increases the rate of Holliday junction (HJ) formation and blocks the cleavage by various types of HJ resolving activities, including the newly identified human GEN1 protein. By using potassium permanganate probing and differential scanning calorimetry, we reveal that the basic domain of TRF2 induces structural changes to the junction. We propose that TRF2 contributes to t‐loop stabilisation by stimulating HJ formation and by preventing resolvase cleavage. These findings provide novel insights into the interplay between telomere protection and homologous recombination and suggest a general model in which TRF2 maintains telomere integrity by controlling the turnover of HJ at t‐loops and at regressed replication forks. 相似文献
167.
Rafael Rodrigues Silva Rafael M. Mariante Andrea Alice Silva Ana Luiza Barbosa dos Santos Ester Roffê Helton Santiago Ricardo Tostes Gazzinelli Joseli Lannes-Vieira 《PloS one》2015,10(2)
The inflammatory cytokine interferon-gamma (IFNγ) is crucial for immunity against intracellular pathogens such as the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (CD). IFNγ is a pleiotropic cytokine which regulates activation of immune and non-immune cells; however, the effect of IFNγ in the central nervous system (CNS) and astrocytes during CD is unknown. Here we show that parasite persists in the CNS of C3H/He mice chronically infected with the Colombian T. cruzi strain despite the increased expression of IFNγ mRNA. Furthermore, most of the T. cruzi-bearing cells were astrocytes located near IFNγ+ cells. Surprisingly, in vitro experiments revealed that pretreatment with IFNγ promoted the infection of astrocytes by T. cruzi increasing uptake and proliferation of intracellular forms, despite inducing increased production of nitric oxide (NO). Importantly, the effect of IFNγ on T. cruzi uptake and growth is completely blocked by the anti-tumor necrosis factor (TNF) antibody Infliximab and partially blocked by the inhibitor of nitric oxide synthesis L-NAME. These data support that IFNγ fuels astrocyte infection by T. cruzi and critically implicate IFNγ-stimulated T. cruzi-infected astrocytes as sources of TNF and NO, which may contribute to parasite persistence and CNS pathology in CD. 相似文献
168.
Juan Bécares Manuel García-Tarrasón Dani Villero Santiago Bateman Lluís Jover Víctor García-Matarranz Carolina Sanpera José Manuel Arcos 《PloS one》2015,10(4)
Although the breeding ecology of Audouin’s gull has been widely studied, its spatial distribution patterns have received little attention. We assessed the foraging movements of 36 GPS-tracked adult Audouin’s gulls breeding at the Ebro Delta (NW Mediterranean), coinciding with the incubation period (May 2011). This also coincided with a trawling moratorium northwards from the colony. We modelled the distribution of the gulls by combining these tracking data with environmental variables (including fishing activities from Vessel Monitoring System, VMS), using Maxent. The modelling range included both marine and terrestrial areas. Models were produced separately for every 2h time interval across the day, and for 2 fishing activity scenarios (workdays vs. weekends), allowing to assess the spatio-temporal distribution patterns of the gulls and the degree of association with fisheries. During workdays, gull distribution at sea fully matched with fishing activities, both trawling (daylight) and purse-seining (nightime). Gulls tended to avoid the area under trawling moratorium, confirming the high influence of fisheries on the distribution patterns of this species. On weekends, gulls made lesser use of the sea and tended to increase the use of rice fields. Overall, Audouin’s gull activity was more intense during dailight hours, although birds also showed nocturnal activity, on both workdays and weekends. Nocturnal patterns at sea were more disperse during the latter, probably because these gulls are able to capture small pelagic fish at night in natural conditions, but tend to congregate around purse-seiners (which would enhance their foraging efficiency) in workdays. These results provide important insight for the management of this species. This is of particular relevance under the current scenario of European fisheries policies, since new regulations are aimed at eliminating discards, and this would likely influence Audouin’s gull populations. 相似文献
169.
Efflux pump‐deficient mutants as a platform to search for microbes that produce antibiotics
下载免费PDF全文
![点击此处可从《Microbial biotechnology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Carlos Molina‐Santiago Zulema Udaondo Abdelali Daddaoua Amalia Roca Jesús Martín Ignacio Pérez‐Victoria Fernando Reyes Juan‐Luis Ramos 《Microbial biotechnology》2015,8(4):716-725
Pseudomonas putida DOT‐T1E‐18 is a strain deficient in the major antibiotic efflux pump (TtgABC) that exhibits an overall increased susceptibility to a wide range of drugs when compared with the wild‐type strain. We used this strain as a platform to search for microbes able to produce antibiotics that inhibit growth. A collection of 2400 isolates from soil, sediments and water was generated and a drop assay developed to identify, via growth inhibition halos, strains that prevent the growth of DOT‐T1E‐18 on solid Luria–Bertani plates. In this study, 35 different isolates that produced known and unknown antibiotics were identified. The most potent inhibitor of DOT‐T1E‐18 growth was an isolate named 250J that, through multi‐locus sequence analysis, was identified as a Pseudomonas sp. strain. Culture supernatants of 250J contain four different xantholysins that prevent growth of Gram‐positive bacteria, Gram‐negative and fungi. Two of the xantholysins were produced in higher concentrations and purified. Xantholysin A was effective against Bacillus, Lysinibacillus and Rhodococcus strains, and the effect against these microbes was enhanced when used in combination with other antibiotics such as ampicillin, gentamicin and kanamycin. Xantholysin C was also efficient against Gram‐positive bacteria and showed an interesting antimicrobial effect against Pseudomonas strains, and a synergistic inhibitory effect with ampicillin, chloramphenicol and gentamicin. 相似文献
170.
Zoraida Verde Luis Reinoso Luis Miguel Chicharro Pilar Resano Ignacio Sánchez-Hernández Jose Miguel Rodríguez González-Moro Fernando Bandrés Félix Gómez-Gallego Catalina Santiago 《PloS one》2015,10(5)
Variations in tobacco-related cancers, incidence and prevalence reflect differences in tobacco consumption in addition to genetic factors. Besides, genes related to lung cancer risk could be related to smoking behavior. Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Common problems in genetic association studies, such as presence of gene-by-environment (G x E) correlation in the population, may reduce the validity of these designs. The main purpose of this study was to evaluate the independence assumption for selected SNPs and smoking behaviour in a cohort of 320 healthy Spanish smokers. We found an association between the wild type alleles of XRCC3 Thr241Met or KLC3 Lys751Gln and greater smoking intensity (OR = 12.98, 95% CI = 2.86–58.82 and OR=16.90, 95% CI=2.09-142.8; respectively). Although preliminary, the results of our study provide evidence that genetic variations in DNA-repair genes may influence both smoking habits and the development of lung cancer. Population-specific G x E studies should be carried out when genetic and environmental factors interact to cause the disease. 相似文献