全文获取类型
收费全文 | 805篇 |
免费 | 85篇 |
出版年
2023年 | 10篇 |
2022年 | 18篇 |
2021年 | 40篇 |
2020年 | 15篇 |
2019年 | 18篇 |
2018年 | 28篇 |
2017年 | 25篇 |
2016年 | 25篇 |
2015年 | 34篇 |
2014年 | 38篇 |
2013年 | 58篇 |
2012年 | 67篇 |
2011年 | 54篇 |
2010年 | 37篇 |
2009年 | 37篇 |
2008年 | 33篇 |
2007年 | 52篇 |
2006年 | 43篇 |
2005年 | 33篇 |
2004年 | 29篇 |
2003年 | 37篇 |
2002年 | 38篇 |
2001年 | 20篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 6篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 2篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1986年 | 4篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1971年 | 1篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1910年 | 1篇 |
排序方式: 共有890条查询结果,搜索用时 484 毫秒
1.
Igor Loncaric Gabrielle L. Stalder Kemal Mehinagic Renate Rosengarten Franz Hoelzl Felix Knauer Chris Walzer 《PloS one》2013,8(12)
In order to test whether rooks (Corvus frugilegus) represent good indicators for the potential circulation of antibiotics in their native habitat, two populations with different migratory behavior were tested for the presence of beta-lactamase producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA). In all, 54 and 102 samples of fresh feces of a migratory and a resident population were investigated. A total of 24 and 3 cefotaxime-resistant enterobacterial isolates were obtained from the migratory and resident population, respectively. In these isolates CTX-M-1 (n = 15), CTX-M-3 (n = 3), and CTX-M-15 (n = 3) genes were detected. TEM-1 and OXA-1 were associated with CTX-M in 3 and 2 isolates, respectively. In two E. coli isolates CMY-2 could be detected, where from one isolate displayed an overexpression of chromosomal AmpC as well. Among E. coli isolates the most common phylogenetic group was A (n = 11) and ST1683 (n = 5). In one E. coli of B2-ST131 the rfbO25b locus was detected. Three Enterobacter isolates were stably derepressed AmpC-producers. In five samples of the migratory population, PVL positive MRSA could be isolated. Two isolates were typed SCCmec IVa, spa type t127, and ST1. Three isolates carried a SCCmec type IVc, with spa type t852 and ST22. The highly significant difference of the occurrence of antibiotic resistance between the migratory population from eastern Europe compared to resident population in our study indicates that rooks may be good indicator species for the evaluation of environmental contamination with antibiotic resistant bacteria, especially due to their ecology, foraging behavior and differing migratory behavior. 相似文献
2.
TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA),
particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness
of TNF inhibitors as initial treatment for active RA. New data from the National Data Bank for Rheumatic Diseases now question
the current consensus in methotrexate failures. The data suggest that in routine clinical practice TNF inhibitors provide
only modest incremental benefits over best conventional therapy. If confirmed, these observational studies suggest that the
economic argument underpinning the widespread use of TNF inhibitors in established RA is unsustainable. 相似文献
3.
Gabrielle C. Winters Gianluca Polese Anna Di Cosmo Leonid L. Moroz 《Journal of morphology》2020,281(7):790-801
Neuropeptide Y (NPY) is an evolutionarily conserved neurosecretory molecule implicated in a diverse complement of functions across taxa and in regulating feeding behavior and reproductive maturation in Octopus. However, little is known about the precise molecular circuitry of NPY-mediated behaviors and physiological processes, which likely involve a complex interaction of multiple signal molecules in specific brain regions. Here, we examined the expression of NPY throughout the Octopus central nervous system. The sequence analysis of Octopus NPY precursor confirmed the presence of both, signal peptide and putative active peptides, which are highly conserved across bilaterians. In situ hybridization revealed distinct expression of NPY in specialized compartments, including potential “integration centers,” where visual, tactile, and other behavioral circuitries converge. These centers integrating separate circuits may maintain and modulate learning and memory or other behaviors not yet attributed to NPY-dependent modulation in Octopus. Extrasomatic localization of NPY mRNA in the neurites of specific neuron populations in the brain suggests a potential demand for immediate translation at synapses and a crucial temporal role for NPY in these cell populations. We also documented the presence of NPY mRNA in a small cell population in the olfactory lobe, which is a component of the Octopus feeding and reproductive control centers. However, the molecular mapping of NPY expression only partially overlapped with that produced by immunohistochemistry in previous studies. Our study provides a precise molecular map of NPY mRNA expression that can be used to design and test future hypotheses about molecular signaling in various Octopus behaviors. 相似文献
4.
Kinga Michno David Knight Jorge M. Campussano Diana van de Hoef Gabrielle L. Boulianne 《PloS one》2009,4(9)
Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the presenilin 1 and 2 genes have been linked to early onset familial forms of Alzheimer''s disease (FAD). Using the Drosophila central nervous system as a model we have investigated the role of presenilin in one of the earliest cellular defects associated with Alzheimer''s disease, intracellular calcium deregulation. We show that expression of either wild type or FAD-mutant presenilin in Drosophila CNS neurons has no impact on resting calcium levels but does give rise to deficits in intracellular calcium stores. Furthermore, we show that a loss-of-function mutation in calmodulin, a key regulator of intracellular calcium, can suppress presenilin-induced deficits in calcium stores. Our data support a model whereby presenilin plays a role in regulating intracellular calcium stores and demonstrate that Drosophila can be used to study the link between presenilin and calcium deregulation. 相似文献
5.
Cutting edge: precursor frequency affects the helper dependence of cytotoxic T cells. 总被引:3,自引:0,他引:3
Justine D Mintern Gayle M Davey Gabrielle T Belz Francis R Carbone William R Heath 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(3):977-980
Generation of CTL immunity often depends on the availability of CD4 T cell help. In this report, we show that CTL responses induced by cross-priming can be converted from CD4-dependent to CD4-independent by increasing the frequency of CTL precursors. In the absence of CD4 T cells, high numbers of CTL precursors were able to expand in number and become effector CTL. The ability of high frequencies of CD8 T cells to override help was not due to their ability to signal CD40 via expression of CD154. These findings suggest that when precursor frequencies are high, priming of CD8 T cell responses may not require CD4 T cell help. 相似文献
6.
Protein Rou. A human IgA hybrid 总被引:1,自引:0,他引:1
E Mihaesco M C Gendron N Congy B Frangione 《Journal of immunology (Baltimore, Md. : 1950)》1988,140(4):1236-1238
Protein Rou is a human IgA2 myeloma protein that carries the isoallotype marker n A2m(2). Partial amino acid sequence of its H chain (alpha) shows that the hinge region and the CH2 domain are homologous to alpha 2-chain and the CH1 and the CH3 domains homologous to alpha 1. Moreover, the CH1 domain contains the H-L disulfide bond identical to alpha 1. It is concluded that Rou H chain is a hybrid molecule caused by a recombination between alpha 1 and alpha 2 genes. The recombination event occurred between alpha 1-exon 1 and alpha 2-exon hinge and corresponds to position 222-223 of the alpha-chain. 相似文献
7.
An excision event that may depend on patchy homology for site specificity. 总被引:2,自引:0,他引:2 下载免费PDF全文
D Bourgaux-Ramoisy D Gendron P Chartrand P Bourgaux 《Molecular and cellular biology》1986,6(7):2727-2730
In mouse cells transformed by a mutant polyomavirus genome, recombination between integrated viral DNA and flanking cellular DNA resulted in the excision of two readily amplifiable chimeras, designated RmI and RmII. The crossing-over that generated RmII was unique in that it involved a simple cellular sequence in which the triplet 5'-CTG-3' was repeated many times. We show that the sequence across the junction resulting from excision was identical in several molecules of RmII, as if the cross-over generating this junction always involved exactly the same two sites on the viral and cellular DNA. We also show that the cellular site mapped where the replacement of a G by an A in one of many successive 5'-CTG-3' triplets generated a homology of five nucleotides (5'-CTACT-3') with the viral site. Oligonucleotides on both sides of these sites are probably involved in matching the two DNAs prior to recombination. 相似文献
8.
Joakim Galli Urban Lendahl Gabrielle Paulsson Christer Ericsson Tomas Bergman Mats Carlquist Lars Wieslander 《Journal of molecular evolution》1990,31(1):40-50
Summary We describe the structure of a gene expressed in the salivary gland cells of the dipteranChironomus tentans and show that it encodes 1 of the approximately 15 secretory proteins exported by the gland cells. This sp115,140 gene consists of approximately 65 copies of a 42-bp sequence in a central uninterrupted core block, surrounded by short nonrepetitive regions. The repeats within the gene are highly similar to each other, but divergent repeats are present in a pattern which suggests that the repeat structure has been remodeled during evolution. The 42-bp repeat in the gene is a simple variant of the more complex repeat unit present in the Balbiani ring genes, encoding four of the other secretory proteins. The structure of the sp115,140 gene suggests that related repeat structures have evolved from a common origin and resulted in the set of genes whose secretory proteins interact in the assembly of the secreted protein fibers. 相似文献
9.
Gabrielle G. Leblanc 《Developmental neurobiology》1990,21(4):567-577
This study shows that explants of quail neural crest cultured in a medium containing serum and chick embryo extract give rise to large numbers of cells expressing immunoreactivity for substance P (SP), a neuropeptide found in sensory neurons. These cells arise from cycling precursors, but do not appear to divide after expressing SP. The SP-positive cells in cranial neural crest cultures express both neurofilament and the Q211 antigen, but those in trunk cultures express only the Q211 antigen. In both cranial and trunk cultures, large subpopulations of the SP-positive cells express tyrosine hydroxylase and/or choline acetyltransferase, neurotransmitter markers characteristic of autonomic neurons. This finding argues against the idea that SP expression necessarily indicates commitment to the sensory neuron lineage. I further show that embryonic dorsal root ganglion (DRG) cells retain the ability to coexpress SP and tyrosine hydroxylase in vitro although to a lesser extent than do neural crest cells. 相似文献
10.
Huili Feng Jiahuan Guo Changhui Peng Daniel Kneeshaw Gabrielle Roberge Chang Pan Xuehong Ma Dan Zhou Weifeng Wang 《Global Change Biology》2023,29(14):3970-3989
A significant increase in reactive nitrogen (N) added to terrestrial ecosystems through agricultural fertilization or atmospheric deposition is considered to be one of the most widespread drivers of global change. Modifying biomass allocation is one primary strategy for maximizing plant growth rate, survival, and adaptability to various biotic and abiotic stresses. However, there is much uncertainty as to whether and how plant biomass allocation strategies change in response to increased N inputs in terrestrial ecosystems. Here, we synthesized 3516 paired observations of plant biomass and their components related to N additions across terrestrial ecosystems worldwide. Our meta-analysis reveals that N addition (ranging from 1.08 to 113.81 g m−2 year−1) increased terrestrial plant biomass by 55.6% on average. N addition has increased plant stem mass fraction, shoot mass fraction, and leaf mass fraction by 13.8%, 12.9%, and 13.4%, respectively, but with an associated decrease in plant reproductive mass (including flower and fruit biomass) fraction by 3.4%. We further documented a reduction in plant root-shoot ratio and root mass fraction by 27% (21.8%–32.1%) and 14.7% (11.6%–17.8%), respectively, in response to N addition. Meta-regression results showed that N addition effects on plant biomass were positively correlated with mean annual temperature, soil available phosphorus, soil total potassium, specific leaf area, and leaf area per plant. Nevertheless, they were negatively correlated with soil total N, leaf carbon/N ratio, leaf carbon and N content per leaf area, as well as the amount and duration of N addition. In summary, our meta-analysis suggests that N addition may alter terrestrial plant biomass allocation strategies, leading to more biomass being allocated to aboveground organs than belowground organs and growth versus reproductive trade-offs. At the global scale, leaf functional traits may dictate how plant species change their biomass allocation pattern in response to N addition. 相似文献