全文获取类型
收费全文 | 3874篇 |
免费 | 299篇 |
出版年
2024年 | 7篇 |
2023年 | 43篇 |
2022年 | 98篇 |
2021年 | 130篇 |
2020年 | 134篇 |
2019年 | 131篇 |
2018年 | 164篇 |
2017年 | 138篇 |
2016年 | 201篇 |
2015年 | 241篇 |
2014年 | 262篇 |
2013年 | 319篇 |
2012年 | 342篇 |
2011年 | 293篇 |
2010年 | 169篇 |
2009年 | 166篇 |
2008年 | 181篇 |
2007年 | 176篇 |
2006年 | 147篇 |
2005年 | 127篇 |
2004年 | 97篇 |
2003年 | 91篇 |
2002年 | 86篇 |
2001年 | 56篇 |
2000年 | 62篇 |
1999年 | 60篇 |
1998年 | 11篇 |
1997年 | 12篇 |
1996年 | 11篇 |
1995年 | 16篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 16篇 |
1991年 | 16篇 |
1990年 | 15篇 |
1989年 | 16篇 |
1988年 | 10篇 |
1987年 | 10篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1980年 | 9篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1971年 | 6篇 |
1968年 | 3篇 |
1967年 | 4篇 |
排序方式: 共有4173条查询结果,搜索用时 31 毫秒
991.
992.
Susana Frases Bruno Pontes Marcio L. Rodrigues Arturo Casadevall 《Biophysical journal》2009,97(4):937-945
Microbial capsules are important for virulence, but their architecture and physical properties are poorly understood. The human pathogenic fungus Cryptococcus neoformans has a large polysaccharide capsule that is necessary for virulence and is the target of protective antibody responses. To study the C. neoformans capsule we developed what we believe is a new approach whereby we probed the capsular elastic properties by applying forces using polystyrene beads manipulated with optical tweezers. This method allowed us to determine the Young's modulus for the capsule in various conditions that affect capsule growth. The results indicate that the Young's modulus of the capsule decreases with its size and increases with the Ca2+ concentration in solution. Also, capsular polysaccharide manifests an unexpected affinity for polystyrene beads, a property that may function in attachment to host cells and environmental structures. Bead probing with optical tweezers provides a new, nondestructive method that may have wide applicability for studying the effects of growth conditions, immune components, and drugs on capsular properties. 相似文献
993.
994.
Andre Rodrigues Rachel N. Cable Ulrich G. Mueller Maurício BacciJr. Fernando C. Pagnocca 《Antonie van Leeuwenhoek》2009,96(3):331-342
We investigate the diversity of yeasts isolated in gardens of the leafcutter ant Atta texana. Repeated sampling of gardens from four nests over a 1-year time period showed that gardens contain a diverse assemblage
of yeasts. The yeast community in gardens consisted mostly of yeasts associated with plants or soil, but community composition
changed between sampling periods. In order to understand the potential disease-suppressing roles of the garden yeasts, we
screened isolates for antagonistic effects against known microfungal garden contaminants. In vitro assays revealed that yeasts
inhibited the mycelial growth of two strains of Escovopsis (a specialized attine garden parasite), Syncephalastrum racemosum (a fungus often growing in gardens of leafcutter lab nests), and the insect pathogen Beauveria bassiana. These garden yeasts add to the growing list of disease-suppressing microbes in attine nests that may contribute synergistically,
together with actinomycetes and Burkholderia bacteria, to protect the gardens and the ants against diseases. Additionally, we suggest that garden immunity against problem
fungi may therefore derive not only from the presence of disease-suppressing Pseudonocardia actinomycetes, but from an enrichment of multiple disease-suppressing microorganisms in the garden matrix. 相似文献
995.
P.G. Coelho P.R. Fernandes H.C. Rodrigues J.B. Cardoso J.M. Guedes 《Journal of biomechanics》2009,42(7):830-837
In this work, a three-dimensional model for bone remodeling is presented, taking into account the hierarchical structure of bone. The process of bone tissue adaptation is mathematically described with respect to functional demands, both mechanical and biological, to obtain the bone apparent density distribution (at the macroscale) and the trabecular structure (at the microscale). At global scale bone is assumed as a continuum material characterized by equivalent (homogenized) mechanical properties. At local scale a periodic cellular material model approaches bone trabecular anisotropy as well as bone surface area density. For each scale there is a material distribution problem governed by density-based design variables which at the global level can be identified with bone relative density. In order to show the potential of the model, a three-dimensional example of the proximal femur illustrates the distribution of bone apparent density as well as microstructural designs characterizing both anisotropy and bone surface area density. The bone apparent density numerical results show a good agreement with Dual-energy X-ray Absorptiometry (DXA) exams. The material symmetry distributions obtained are comparable to real bone microstructures depending on the local stress field. Furthermore, the compact bone porosity is modeled giving a transversal isotropic behavior close to the experimental data. Since, some computed microstructures have no permeability one concludes that bone tissue arrangement is not a simple stiffness maximization issue but biological factors also play an important role. 相似文献
996.
Fernanda Bernardes Calvo Dário Santos Junior Consuelo Junqueira Rodrigues Francisco José Krug Júlio Takehiro Marumo Nestor Schor Maria Helena Bellini 《Biological trace element research》2009,130(2):107-113
The development of cancer is a complex, multistage process during which a normal cell undergoes genetic changes that result
in phenotypic alterations and in the acquisition of the ability to invade other sites. Inductively coupled plasma optical
emission spectroscopy was used to estimate the contents of Al, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, P, Pb, and Zn in healthy
kidney and renal cell carcinoma (RCC), and significant differences were found for all elements. Along with the progression
of the malignant disease, a progressive decrease of Cd and K was observed. In fact, for Cd, the concentration in stage T4
was 263.9 times lower than in stage T1, and for K, the concentration in stage T4 was 1.73 times lower than in stage T1. Progressive
accumulation was detected for P, Pb, and Zn in stage T4. For P, the concentration in stage T4 was 11.1 times higher than in
stage T1; for Pb, the concentration in stage T4 was 232.7 times higher than in T1; and for Zn, the concentration in T4 was
8.452 times higher than in T1. This study highlights the marked differences in the concentrations of selected trace metals
in different malignant tumor stages. These findings indicate that some trace metals may play important roles in the pathogenesis
of RCC. 相似文献
997.
Rodrigues M Fernandes CA Palomares F Amorim IR Bruford MW Santos-Reis M 《Molecular ecology resources》2009,9(4):1205-1208
We report the isolation of 11 polymorphic tetranucleotide microsatellite loci in the Egyptian mongoose (Herpestes ichneumon). In a sample of 27 individuals, we observed between 4 and 7 alleles per locus and their observed and expected heterozygosities ranged from 0.37 to 0.85 and from 0.44 to 0.79, respectively. All genotypic frequencies conformed to Hardy-Weinberg equilibrium expectations and there were no instances of linkage disequilibrium detected between pairs of loci. 相似文献
998.
Background
Potentially chloroquine resistant P. falciparum, identified by the 76T haplotype in the chloroquine resistance transporter (pfcrt 76T), are highly prevalent throughout Africa. In Guinea-Bissau, normal and double dose chloroquine have respective efficacies of 34% and 78% against P.falciparum with pfcrt 76T and approximately three times the normal dose of chloroquine is routinely taken. Proportions of pfcrt 76T generally increase during high transmission seasons, as P.falciparum with pfcrt 76T commonly survive treatment with normal dose chloroquine. In Guinea-Bissau, there should be no seasonal increase of pfcrt 76T if the high doses of CQ commonly used are effective.Methods and Findings
P. falciparum parasite density, age, sex, the proportion of chloroquine resistance associated haplotypes pfcrt 76T and P. falciparum multidrug resistance gene 1 86Y were assessed in 988 samples collected from children between 2002 and 2007. There was no seasonal accumulation of any allele. During the high and low transmission periods the pfcrt 76T proportions were 24% (95% CI, 21–27%) and 26% (95% CI, 20–33%). There was no significant change of pfcrt 76T (OR 1.05, 95% CI; 0.94–1.16 p = 0.39) or pfmdr1 86Y (OR 0.92, 95%CI; 0.83–1.01 p = 0.08) proportions between 2003 and 2007. Lower median parasite density (P.falciparum/µl) was associated with pfcrt 76T (15254 [95% CI, 12737–17772]; n = 164) compared to pfcrt 76K (18664 [95% CI, 16676–20653]; p = 0.003; n = 591). Similarly, pfmdr1 86Y was associated with a lower median parasite density (16320 [95% CI, 13696–18944]; n = 224) compared to pfmdr1 86N, (18880 [95% CI, 16701–21059]; P = 0.018; n = 445).Conclusions
In contrast to the rest of Africa, P. falciparum parasites resistant to normal dose chloroquine do not have a selective advantage great enough to become the dominant P.falciparum type in Guinea-Bissau. This is most likely due to the efficacy of high-dose chloroquine as used in Guinea-Bissau, combined with a loss of fitness associated with pfcrt 76T. 相似文献999.
Ana Martins Gabriella Spengler Liliana Rodrigues Miguel Viveiros Jorge Ramos Marta Martins Isabel Couto Séamus Fanning Jean-Marie Pagès Jean Michel Bolla Joseph Molnar Leonard Amaral 《PloS one》2009,4(8)
Background
Resistance Nodulation Division (RND) efflux pumps of Escherichia coli extrude antibiotics and toxic substances before they reach their intended targets. Whereas these pumps obtain their energy directly from the proton motive force (PMF), ATP-Binding Cassette (ABC) transporters, which can also extrude antibiotics, obtain energy from the hydrolysis of ATP. Because E. coli must pass through two pH distinct environments of the gastrointestinal system of the host, it must be able to extrude toxic agents at very acidic and at near neutral pH (bile salts in duodenum and colon for example). The herein described study examines the effect of pH on the extrusion of ethidium bromide (EB).Methodology/Principal Findings
E. coli AG100 and its tetracycline induced progeny AG100TET that over-expresses the acrAB efflux pump were evaluated for their ability to extrude EB at pH 5 and 8, by our recently developed semi-automated fluorometric method. At pH 5 the organism extrudes EB without the need for metabolic energy (glucose), whereas at pH 8 extrusion of EB is dependent upon metabolic energy. Phe-Arg β-naphtylamide (PAβN), a commonly assumed inhibitor of RND efflux pumps has no effect on the extrusion of EB as others claim. However, it does cause accumulation of EB. Competition between EB and PAβN was demonstrated and suggested that PAβN was preferentially extruded. A Km representing competition between PAβN and EB has been calculated.Conclusions/Significance
The results suggest that E. coli has two general efflux systems (not to be confused with a distinct efflux pump) that are activated at low and high pH, respectively, and that the one at high pH is probably a putative ABC transporter coded by msbA, which has significant homology to the ABC transporter coded by efrAB of Enterococcus faecalis, an organism that faces similar challenges as it makes its way through the toxic intestinal system of the host. 相似文献1000.
Claucia Fernanda Volken de Souza Rafael Costa Rodrigues Marco Antônio Záchia Ayub 《Biotechnology and Bioprocess Engineering》2009,14(5):571-576
The effects of oxygenation in cultures of Bacillus circulans BL32 on transglutaminase (TGase) production and cell sporulation were studied by varying the agitation speed and the volume
of aeration. Kinetics of cultivations has been studied in batch systems using a 2 L bioreactor, and the efficiency of agitation
and aeration was evaluated through the oxygen volumetric mass transfer coefficient (kLa). It was adopted a two-stage aeration rate control strategy: first stage to induce biomass formation, followed by a second
stage, in which cell sporulation was stimulated. A correlation of TGase production, spores formation, and oxygen concentration
was established. Under the best conditions (500 rpm; 2 vvm air flow, followed by no air supply during stationary phase; kLa of 33.7 h−1), TGase production reached a volumetric production of 589 U/L after 50 h of cultivation and the enzyme yield was 906 U/g
cells. These values are 61% higher than that obtained in shaker cultures and TGase productivity increased 82%, when kLa varied from 4.4 to 33.7 h−1. The maximal cell concentration increased four times in relation to shaker cultures and the cultivation time for the highest
TGase activity was reduced from 192 h to just 50 h. These results show the importance of bioprocess design for the production
of microbial TGase, especially concerning the oxygen supply of cultures and the induction of cell sporulation. 相似文献