全文获取类型
收费全文 | 1032篇 |
免费 | 50篇 |
专业分类
1082篇 |
出版年
2023年 | 14篇 |
2022年 | 21篇 |
2021年 | 31篇 |
2020年 | 17篇 |
2019年 | 26篇 |
2018年 | 29篇 |
2017年 | 27篇 |
2016年 | 34篇 |
2015年 | 53篇 |
2014年 | 48篇 |
2013年 | 74篇 |
2012年 | 75篇 |
2011年 | 76篇 |
2010年 | 43篇 |
2009年 | 34篇 |
2008年 | 52篇 |
2007年 | 43篇 |
2006年 | 37篇 |
2005年 | 36篇 |
2004年 | 30篇 |
2003年 | 23篇 |
2002年 | 18篇 |
2001年 | 20篇 |
2000年 | 17篇 |
1999年 | 18篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 16篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 19篇 |
1988年 | 7篇 |
1987年 | 10篇 |
1986年 | 4篇 |
1985年 | 10篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 7篇 |
1975年 | 5篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1966年 | 3篇 |
排序方式: 共有1082条查询结果,搜索用时 0 毫秒
31.
Ravi Tandon Maria T. M. Giret Devi SenGupta Vanessa A. York Andrew A. Wiznia Michael G. Rosenberg Esper G. Kallas Lishomwa C. Ndhlovu Douglas F. Nixon 《PloS one》2012,7(9)
As perinatally HIV-1-infected children grow into adolescents and young adults, they are increasingly burdened with the long-term consequences of chronic HIV-1 infection, with long-term morbidity due to inadequate immunity. In progressive HIV-1 infection in horizontally infected adults, inflammation, T cell activation, and perturbed T cell differentiation lead to an “immune exhaustion”, with decline in T cell effector functions. T effector cells develop an increased expression of CD57 and loss of CD28, with an increase in co-inhibitory receptors such as PD-1 and Tim-3. Very little is known about HIV-1 induced T cell dysfunction in vertical infection. In two perinatally antiretroviral drug treated HIV-1-infected groups with median ages of 11.2 yr and 18.5 yr, matched for viral load, we found no difference in the proportion of senescent CD28−CD57+CD8+ T cells between the groups. However, the frequency of Tim-3+CD8+ and Tim-3+CD4+ exhausted T cells, but not PD-1+ T cells, was significantly increased in the adolescents with longer duration of infection compared to the children with shorter duration of HIV-1 infection. PD-1+CD8+ T cells were directly associated with T cell immune activation in children. The frequency of Tim-3+CD8+ T cells positively correlated with HIV-1 plasma viral load in the adolescents but not in the children. These data suggest that Tim-3 upregulation was driven by both HIV-1 viral replication and increased age, whereas PD-1 expression is associated with immune activation. These findings also suggest that the Tim-3 immune exhaustion phenotype rather than PD-1 or senescent cells plays an important role in age-related T cell dysfunction in perinatal HIV-1 infection. Targeting Tim-3 may serve as a novel therapeutic approach to improve immune control of virus replication and mitigate age related T cell exhaustion. 相似文献
32.
Spatial distribution of root activity and nitrogen fixation in sorghum/pigeonpea intercropping on an Indian Alfisol 总被引:2,自引:0,他引:2
Ito Osamu Matsunaga Ryoichi Tobita Satoshi Rao Theertham P. Devi Y. Gayatri 《Plant and Soil》1993,155(1):341-344
A medium-duration pigeonpea cultivar (ICP 1–6) and a hybrid sorghum (CSH 5) were grown on a shallow Alfisol in monocropping and intercropping systems. Using a monolith method, spatial distribution of nodulation, acetylene reduction activity (ARA) and root respiration were measured.The number, mass and ARA of nodules decreased exponentially with distance from the plant base except at the late reproductive stage. Nodulation and ARA tended to be higher in the intercrop than in the monocrop.Respiration rate of roots increased with distance from the plant base and reached a maximum value at about 20–30 cm. The rate was higher in pigeonpea than in sorghum and also higher in intercrop than in monocrop.This study suggests that pigeonpea roots are physiologically more active than sorghum roots, implying that pigeonpea may become a strong competitor for nutrients in the soil when intercropped. The nitrogen-fixing ability of pigeonpea may be enhanced by intercropping because the sorghum rapidly absorbed inorganic N which would otherwise inhibit N2 fixation. 相似文献
33.
U.S. Aswathy Rajeev K. Sukumaran G. Lalitha Devi K.P. Rajasree Reeta Rani Singhania Ashok Pandey 《Bioresource technology》2010,101(3):925-930
Biomass feedstock having less competition with food crops are desirable for bio-ethanol production and such resources may not be localized geographically. A distributed production strategy is therefore more suitable for feedstock like water hyacinth with a decentralized availability. In this study, we have demonstrated the suitability of this feedstock for production of fermentable sugars using cellulases produced on site. Testing of acid and alkali pretreatment methods indicated that alkali pretreatment was more efficient in making the sample susceptible to enzyme hydrolysis. Cellulase and β-glucosidase loading and the effect of surfactants were studied and optimized to improve saccharification. Redesigning of enzyme blends resulted in an improvement of saccharification from 57% to 71%. A crude trial on fermentation of the enzymatic hydrolysate using the common baker’s yeast Saccharomyces cerevisiae yielded an ethanol concentration of 4.4 g/L. 相似文献
34.
N-glycolylneuraminic acid (Neu5Gc) is one of the two most common forms of sialic acids present in glycoproteins and glycolipids of mammalian tissues. It is synthesized from the most ubiquitous sialic acid, N-acetylneuraminic acid (Neu5Ac) in a hydroxylation reaction catalysed by the enzyme Neu5Ac hydroxylase. Though Neu5Gc conjugates are prevalent in many tissues of mammals, they are absent in glycolipids and only trace amounts are present in glycoproteins of the brain and central nervous system. In humans Neu5Ac is the main sialic acid as Neu5Ac hydroxylase is inactive due to mutation of its gene. The importance of sialic acids in biochemical phenomena and the distinct roles played by specific forms of these amino sugars is adequately reflected in functional studies of selectin and sialoadhesin families of adhesion molecules. The absence of Neu5Gc, therefore, in tissues of humans and brain of mammals has raised interest, especially with regard to its impact on biochemical differences evident between humans and other mammals. It is suggested that though Neu5Gc conjugates are important in cellular interactions, their presence in brain and the central nervous system is deleterious to the latter's normal functions. Their interaction with other cellular components to form supramolecular associations is indicated that may have a bearing on major biochemical differences, a few of which are presently evident between humans and other mammals. 相似文献
35.
The ratio of gelatin to sodium carboxymethyl cellulose (SCMC) at which maximum yield was obtained was optimized. This optimized
ratio of gelatin to SCMC along with other parameters was used to prepare microparticles of different sizes. Vegetable oil
was used as emulsion medium. Effect of various factors like amount of surfactant, concentration of polymer on the formation,
and size of the microparticles was investigated. These microparticles were used as carrier for isoniazid. Among different
cross-linkers, glutaraldehyde was found to be the most effective cross-linker at the temperature and pH at which the reaction
was carried out. The loading efficiency and release behavior of loaded microparticles were found to be dependent on the amount
of cross-linker used, concentration of drug, and time of immersion. Maximum drug loading efficiency was observed at higher
immersion time. The release rate of isoniazid was more at higher pH compared to that of at lower pH. The sizes of the microparticles
were investigated by scanning electron microscope. In all the cases, the microparticles formed were found spherical in shape
except to those at low stirring speed where they were agglomerated. Fourier transform infrared study indicated the successful
incorporation of isoniazid into the microparticles. Differential scanning calorimetry study showed a molecular level dispersion
of isoniazid in the microparticles. X-ray diffraction study revealed the development of some crystallinity due to the encapsulation
of isoniazid. 相似文献
36.
37.
In spite of the rapid advances in the development of the new proteomic technologies, there are, to date, relatively fewer studies aiming to explore the neuronal proteome. One of the reasons is the complexity of the brain, which presents high cellular heterogeneity and a unique subcellular compartmentalization. Therefore, tissue fractionation of the brain to enrich proteins of interest will reduce the complexity of the proteomics approach leading to the production of manageable and meaningful results. In this review, general considerations and strategies of proteomics, the advantages and challenges to exploring the neuronal proteome are described and summarized. In addition, this article presents an overview of recent advances of proteomic technologies and shows that proteomics can serve as a valuable tool to globally explore the changes in brain proteome during various disease states. Understanding the molecular basis of brain function will be extremely useful in identifying novel targets for the treatment of brain diseases. 相似文献
38.
Kranthi Kumar Konidala Uma Devi Bommu 《Journal of receptor and signal transduction research》2013,33(4):372-383
AbstractIn this study, binding efficiency of new pyrrolopyrimidine structural analogs against human vascular endothelial growth factor receptor-2 (VEGFR-2) were elucidated using integrated in silico methods. Optimized high-resolution model of VEGFR-2 was generated and adopted for structure-based virtual screening approaches. Pyrrolopyrimidine inhibitor (CP15) associated compounds were screened from PubChem database and subjected to virtual screening and comparative docking methods against the receptor ligand-binding domain. Accordingly, high efficient compounds were clustered with similarity indices through PubChem structure cluster module using single-linkage algorithm. Moreover, pharmacokinetics including drug metabolism activities of high-binding leads under investigation was portrayed using ADMET and similarity ensemble analysis. Optimal energy orientations of the selected protein model have been shown to be reliable, and highly recommended for screening and docking studies. Docking and clustering strategies were shown that nineteen candidates as most effective binders for VEGFR-2 than CP15, and are grouped as three classes. Lys868, Glu885, Cys919, His1026, Arg1027, Asp1046, and Gly1048 residues were predicted as novel hotspot residues, and participate in H-bonds, π-cation, π-stacking, halogen bonds, and salt-bridges formation with ligands. These additional bonds are contributing extent stability that holds the receptor structure at flexible state, this make difficult to any further conformational changes for evoking angiogenic signals. The ADMET and similarity ensemble analysis results were strongly indicated that thirteen candidates as best ligands for angiogenesis targets. Altogether, these findings indicate potential angiogenic templates and their binding levels with VEGFR-2; sorted viewpoints could be useful as a promising way to describe potential angiogenesis inhibitors with related molecular targets. 相似文献
39.
40.
Y. L. Nandadeva C. G. Lupi C. S. Meyer P. S. Devi I. Potrykus R. Bilang 《Plant cell reports》1999,18(6):500-504
Microprojectile-mediated transient and integrative transformation frequencies in rice (Oryza sativa cv. Taipei 309) embryogenic suspension cells were studied as a function of various parameters. Mannitol at concentrations
of 0.5 and 0.6 m was best for osmotic preconditioning of the cells for transient, but not for integrative transformation, for which sucrose
yielded the best and most reliable results. Denaturation of the transforming plasmid DNA prior to bombardment improved transient
and integrative transformation frequencies two to three fold. Delivery of double-stranded plasmids in linear form had no effect
on transient transformation when compared to supercoiled plasmid DNA, but led to an overall two fold increase in integrative
transformation frequency. This shows that optimized protocols for generating transgenic plants should not be based exclusively
on transient gene expression assays.
Received: 29 September 1997 / Revision received: 27 February 1998 / Accepted: 2 April 1998 相似文献