首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   5828篇
  免费   453篇
  国内免费   4篇
  6285篇
  2023年   30篇
  2022年   77篇
  2021年   148篇
  2020年   85篇
  2019年   99篇
  2018年   170篇
  2017年   138篇
  2016年   195篇
  2015年   269篇
  2014年   303篇
  2013年   366篇
  2012年   468篇
  2011年   488篇
  2010年   269篇
  2009年   249篇
  2008年   336篇
  2007年   357篇
  2006年   335篇
  2005年   274篇
  2004年   232篇
  2003年   243篇
  2002年   215篇
  2001年   61篇
  2000年   55篇
  1999年   53篇
  1998年   41篇
  1997年   34篇
  1996年   26篇
  1995年   25篇
  1994年   29篇
  1993年   23篇
  1992年   31篇
  1991年   24篇
  1990年   28篇
  1989年   42篇
  1988年   22篇
  1987年   15篇
  1986年   30篇
  1985年   34篇
  1984年   33篇
  1983年   27篇
  1982年   22篇
  1981年   19篇
  1980年   14篇
  1979年   14篇
  1978年   19篇
  1977年   15篇
  1976年   20篇
  1975年   12篇
  1974年   16篇
排序方式: 共有6285条查询结果,搜索用时 15 毫秒
991.
Rodent species were assessed as potential hosts of Trypanosoma cruzi, the etiologic agent of Chagas disease, from five sites throughout Texas in sylvan and disturbed habitats. A total of 592 rodents were captured, resulting in a wide taxonomic representation of 11 genera and 15 species. Heart samples of 543 individuals were successfully analyzed by SybrGreen-based quantitative PCR (qPCR) targeting a 166 bp fragment of satellite DNA of T. cruzi. Eight rodents representing six species from six genera and two families were infected with T. cruzi. This is the first report of T. cruzi in the pygmy mouse (Baiomys taylori) and the white-footed mouse (Peromyscus leucopus) for the USA. All infected rodents were from the southernmost site (Las Palomas Wildlife Management Area). No differences in pathogen prevalence existed between disturbed habitats (5 of 131 tested; 3.8%) and sylvan habitats (3 of 40 tested; 7.5%). Most positives (n = 6, 16% prevalence) were detected in late winter with single positives in both spring (3% prevalence) and fall (1% prevalence). Additionally, 30 Triatoma insects were collected opportunistically from sites in central Texas. Fifty percent of these insects, i.e., 13 T. gerstaeckeri (68%), and two T. lecticularia (100%) were positive for T. cruzi. Comparative sequence analyses of 18S rRNA of samples provided identical results with respect to detection of the presence or absence of T. cruzi and assigned T. cruzi from rodents collected in late winter to lineage TcI. T. cruzi from Triatoma sp. and rodents from subsequent collections in spring and fall were different, however, and could not be assigned to other lineages with certainty.  相似文献   
992.
Rapid improvement in photoconversion efficiency (PCE) of solution processable organometallic hybrid halide based perovskite solar cells (PSCs) have taken the photovoltaic (PV) community with a surprise and has extended their application in other electronic devices such as light emitting diodes, photo detectors and batteries. Together with efforts to push the PCE of PSCs to record values >22% – now at par with that of crystalline silicon solar cells – origin of their PV action and underlying physical processes are also deeply investigated worldwide in diverse device configurations. A typical PSC consists of a perovskite film sandwiched between an electron and a hole selective contact thereby creating ESC/perovskite and perovskite/HSC interfaces, respectively. The selective contacts and their interfaces determine properties of perovskite layer and also control the performance, origin of PV action, open circuit voltage, device stability, and hysteresis in PSCs. Herein, we define ideal charge selective contacts, and provide an overview on how the choice of interfacing materials impacts charge accumulation, transport, transfer/recombination, band‐alignment, and electrical stability in PSCs. We then discuss device related considerations such as morphology of the selective contacts (planar or mesoporous), energetics and electrical properties (insulating and conducting), and its chemical properties (organic vs inorganic). Finally, the outlook highlights key challenges and future directions for a commercially viable perovskite based PV technology.  相似文献   
993.
Nanostructured V2O5 is emerging as a new cathode material for lithium ion batteries for its distinctly high theoretic capacity over the current commercial cathodes. The main challenges associated with nanostructured V2O5 cathodes are structural degradation, instability of the solid‐electrolyte interface layer, and poor electron conductance, which lead to low capacity and rapid decay of cyclic stability. Here, a novel composite structure of V2O5 nanoparticles encapsulated in 3D networked porous carbon matrix coated on carbon fibers (V2O5/3DC‐CFs) is reported that effectively addresses the mentioned problems. Remarkably, the V2O5/3DC‐CF electrode exhibits excellent overall lithium‐storage performance, including high Coulombic efficiency, excellent specific capacity, outstanding cycling stability and rate property. A reversible capacity of ≈183 mA h g?1 is obtained at a high current density of 10 C, and the battery retains 185 mA h g?1 after 5000 cycles, which shows the best cycling stability reported to date among all reported cathodes of lithium ion batteries as per the knowledge. The outstanding overall properties of the V2O5/3DC‐CF composite make it a promising cathode material of lithium ion batteries for the power‐intensive energy storage applications.  相似文献   
994.
We investigate how perturbations that induce mortality transform original spatial patterns in plant communities into binary spatial patterns of survivors and perished individuals. By means of computer simulation, we analyse effects of average mortality, interspecific variation of mortality around the mean, spatial distribution of the species (clumping degree), and species richness. Gap spatial pattern is quantified by four spatial indices or landscape metrics (gap area, density, shape and coherence). In single‐species communities, the emerging gap patterns are subject to critical phenomena: opportunities for colonizers to establish increase with mortality, but more rapidly at specific mortality thresholds. In multi‐species communities, neither species richness nor interspecific variation of mortality influences gap spatial pattern when community assembly is random. Colonization opportunities would therefore not be affected by local species extinction in such a system, nor by the presence of species with divergent sensitivities to perturbation. In a community that is highly spatially aggregated, increases in interspecific mortality variation shift the pattern towards fewer gaps that are larger and more isodiametric, which suggests increased establishment chances for colonizers. Similar changes are induced in communities characterized by large interspecific mortality differences if clumping degree is increased. Loss of species richness only modifies gap spatial pattern to a substantial extent if mortality variation is high: in this case, depauperate communities exhibit a wider variety of colonization opportunities (more gaps which are on average smaller, but the largest gap is larger) than species‐richer ones. These findings may explain the contrast between the negative diversity‐invasibility relationship often found in small‐scale experimental studies and the positive diversity‐invasibility relationship found in observational studies at larger scale. They also demonstrate that the pre‐disturbance spatial structure of a community significantly affects colonization opportunities for alien species, and is therefore a likely determinant of the trajectory of secondary succession following perturbation.  相似文献   
995.
Evaluation of an FRDA–EGFP genomic reporter assay in transgenic mice   总被引:2,自引:0,他引:2  
Friedreich ataxia is an autosomal recessive neurodegenerative disorder caused by a GAA trinucleotide expansion in the first intron of the Friedreich ataxia gene (FRDA) that causes reduced synthesis of frataxin, a mitochondrial protein likely to be involved in biosynthesis of iron–sulfur clusters. This leads to increased oxidative stress, progressive loss of large sensory neurons, and hypertrophic cardiomyopathy. To elucidate the mechanisms regulating FRDA expression and to develop an in vivo assay for agents that might upregulate FRDA expression in a therapeutically relevant manner, we have generated transgenic mice with a BAC genomic reporter construct consisting of an in-frame fusion between FRDA and the gene coding for enhanced green fluorescent protein (EGFP). Production of full-length frataxin–EGFP fusion protein was demonstrated by immunoblotting. EGFP expression was observed as early as day E3.5 of development. Most tissues of adult transgenic mice were fluorescent. The level of FRDAEGFP expression in peripheral blood, bone marrow, and cells obtained from enzymatically disaggregated tissues was quantitated by flow cytometry. There was a twofold increase in EGFP expression in mice homozygous for the transgene when compared to hemizygous mice. These transgenic mice are a valuable tool for the examination of spatial and temporal aspects of FRDA gene expression and for the preclinical evaluation of pharmacological inducers of FRDA expression in a whole-animal model. In addition, tissues from these mice should also be valuable for stem cell transplantation studies.  相似文献   
996.
Despite the lack of direct cytogenetic studies, the neuronal cells of the normal human brain have been postulated to contain normal (diploid) chromosomal complement. Direct proof of a chromosomal mutation presence leading to large-scale genomic alterations in neuronal cells has been missing in the human brain. Large-scale genomic variations due to chromosomal complement instability in developing neuronal cells may lead to the variable level of chromosomal mosaicism probably having a substantial effect on brain development. The aim of the present study was the pilot assessment of chromosome complement variations in neuronal cells of developing and adult human brain tissues using interphase multicolor fluorescence in situ hybridization (mFISH). Chromosome-enumerating DNA probes from the original collection (chromosomes 1, 13 and 21, 18, X, and Y) were used for the present pilot FISH study. As a source of fetal brain tissue, the medulla oblongata was used. FISH studies were performed using uncultured fetal brain samples as well as organotypic cultures of medulla oblongata tissue. Cortex tissues of postmortem adult brain samples (Brodmann area 10) were also studied. In cultured in vitro embryonic neuronal brain cells, an increased level of aneuploidy was found (mean rate in the range of 1.3-7.0% per individual chromosome, in contrast to 0.6-3.0% and 0.1-0.8% in uncultured fetal and postmortem adult brain cells, respectively). The data obtained support the hypothesis regarding aneuploidy occurrence in normal developing and adult human brain.  相似文献   
997.
Dzherelo (Immunoxel) and Anemin when combined with standard anti-tuberculosis therapy (ATT) were shown to produce better clinical outcome than chemotherapy alone. Sixty HIV-positive patients with active pulmonary TB were equally divided into three matched groups to receive either ATT, ATT + Dzherelo, or ATT + Dzherelo + Anemin. Peripheral blood samples were measured by ELISA for plasma levels of IL-2, IL-6, TNF-α, IFN-γ, and IFN-α. After 6 months of follow-up Dzherelo and Dzherelo + Anemin combinations produced 61% (P = 0.005) and 44.4% (P = 0.06) higher levels of IL-2, whereas in ATT group they were reduced by 33.1% (P = 0.002). The levels of IL-6 increased by 17% (P = 0.15) in ATT group, but declined in both immune intervention groups by 26.2% (P = 0.007) and 21.3% (P = 0.22). TNF-α was suppressed in two immunotherapy groups by 19.1% (P = 0.06) and 76.3% (P = 0.02), respectively, but had risen by 14% (P = 0.42) in ATT patients. The pattern of production of IFN-γ was opposite to that of TNF-α, but statistical significance was stronger in patients receiving ATT and Dzherelo + Anemin than in Dzherelo group: −34% (P = 0.004), +31.9% (P = 0.008), and +17.3% (P = 0.33), respectively. Moderately decreased levels of IFN-α were observed in all treatment arms (range 0.9–16.6%) but differences were not significant. Despite considerable intra-group variation in cytokine production, the baseline inter-group averages were not statistically different indicating that the results were not biased by sample heterogeneity. Immunomodulators used in this study possibly act by enhancing natural immune response against TB. Expanded study of other cytokines and correlates relevant to control and protection from TB and HIV is needed in order to identify biomarkers of favorable treatment outcome, which may aid design of better immune interventions and vaccines.  相似文献   
998.
Centrifugal dehydration force (CDF) and rehydration isotherm (RHI) methods were used to measure and characterize hydration fractions in rabbit psoas skeletal muscle. The CDF method assessed fluid flow rate from rabbit muscle and hydration capacity of the fractions. Bulk and multiple non-bulk water fractions were identified. The non-bulk water was divisible into the following fractions: two outer non-bulk fractions, a main chain proteins backbone or double water bridge fraction, and a single water bridge fraction. The total non-bulk water amounts to about 85% of the total water in the muscle. The sizes of the water fractions (in g water/g dry mass) agree with a recently proposed molecular stoichiometric hydration model (SHM) applicable to all proteins in and out of cells (Fullerton GD, Cameron IL. Water compartments in cells. Methods Enzymol, 2007; Cameron IL, Fullerton GD. Interfacial water compartments on tendon/collagen and in cells. In: Pollack GH, Chin WC, editors. Phase transitions in cells. Dordrecht, The Netherlands: Springer, 2008). Age of the rabbit significantly slowed the flow rate of the outer non-bulk water fraction by about 50%. Also, muscle of the older rabbit (26 weeks vs. 12 weeks old) had less bulk water and less outer non-bulk water but the same amount of main chain backbone water compared to muscle of the younger rabbit. Increase in time post-mortem from 30min to 4h resulted in rigor mortis and a significantly slower flow rate of water from the outer non-bulk water fraction, which is attributed to muscle contraction, increased packing of contractile elements and increased obstructions to flow of fluid from the muscle fibers.  相似文献   
999.
The melanocortin (MC) receptor type-1 (MC1-R) is the only one of the five MC receptor subtypes expressed in human adipose tissue explants, human mesenchymal stem cells (MSCs), and MSC-derived adipocytes. Following our recent expression studies (Obesity 2007, 15, 40-49), we now investigated the functional role of MC1-R in these tissues and cells to deduce the coupling state of MC1-R to intracellular output signals in human fat cells and tissue. Expression of MC1-R by undifferentiated and differentiated MSCs was quantified by real-time TaqMan PCR. Intracellular output signals (cAMP, lipolysis, secretion of IL-6, IL-10, and TNF-alpha), as well as effects on the metabolic rate and proliferation of human MSCs were analyzed by standard assays, exposing undifferentiated and differentiated MSCs and, in part, human adipose tissue explants to the potent MC1-R agonist, [Nle(4), D-Phe(7)]-alpha-MSH (NDP-MSH). This agonist induced a weak cAMP signal in MSC-derived adipocytes. However, it did not affect lipolysis in these cells or in adipose tissue explants, nor did it modulate cytokine release and mRNA expression of IL-6, IL-8, and TNF-alpha upon LPS stimulation. In undifferentiated MSCs, NDP-MSH did not alter the metabolic rate, but it showed a significant antiproliferative effect. Therefore, it appears that MC1-R-effector coupling in (differentiated) human adipocytes is too weak to induce a regulatory effect on lipolysis or inflammation; by contrast, MC1-R stimulation in undifferentiated MSCs induces an inhibitory signal on cell proliferation.  相似文献   
1000.
Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by genetic and environmental factors. Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an important component of the lung tissue homeostasis, involved in the regulation of the rate of mucociliary clearance. As it is known that certain CFTR variants have consequences on the function of CFTR protein, the aim of this study was to examine the possible role of F508del, M470V, Tn locus, and R75Q variants in COPD development and modulation. Total number of 86 COPD patients and 102 control subjects were included in the study. Possible association between COPD susceptibility, severity, and onset of the disease and allele or genotype of four analyzed CFTR variants was examined. No associations were detected between COPD development, onset of the disease and tested CFTR alleles and genotypes. However, VV470 genotype was associated with mild/moderate COPD stages in comparison to severe/very severe ones (OR = 0.29, 95%CI = 0.11-0.80, p = 0.016). Our study showed that patients with VV470 genotype had a 3.4-fold decreased risk for the appearance of severe/very severe COPD symptoms, and the obtained results indicate that this genotype may have a protective role. These results also suggest the importance of studying CFTR gene as a modifier of this disease.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号