全文获取类型
收费全文 | 5686篇 |
免费 | 410篇 |
专业分类
6096篇 |
出版年
2024年 | 7篇 |
2023年 | 22篇 |
2022年 | 71篇 |
2021年 | 103篇 |
2020年 | 51篇 |
2019年 | 90篇 |
2018年 | 131篇 |
2017年 | 104篇 |
2016年 | 166篇 |
2015年 | 231篇 |
2014年 | 294篇 |
2013年 | 442篇 |
2012年 | 468篇 |
2011年 | 462篇 |
2010年 | 290篇 |
2009年 | 221篇 |
2008年 | 363篇 |
2007年 | 356篇 |
2006年 | 337篇 |
2005年 | 339篇 |
2004年 | 298篇 |
2003年 | 245篇 |
2002年 | 264篇 |
2001年 | 62篇 |
2000年 | 59篇 |
1999年 | 66篇 |
1998年 | 60篇 |
1997年 | 42篇 |
1996年 | 50篇 |
1995年 | 44篇 |
1994年 | 31篇 |
1993年 | 46篇 |
1992年 | 32篇 |
1991年 | 18篇 |
1990年 | 20篇 |
1989年 | 18篇 |
1988年 | 16篇 |
1987年 | 19篇 |
1986年 | 16篇 |
1985年 | 14篇 |
1984年 | 26篇 |
1983年 | 14篇 |
1982年 | 7篇 |
1981年 | 15篇 |
1980年 | 11篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1972年 | 6篇 |
1971年 | 5篇 |
排序方式: 共有6096条查询结果,搜索用时 15 毫秒
991.
992.
Saino Nicola; Ambrosini Roberto; Martinelli Roberta; Ninni Paola; Moller Anders Pape 《Behavioral ecology》2003,14(1):16-22
In some passerines, parents allocate more food to offspringwith the brightest red gapes, but the function of parental decisionsbased on offspring gape coloration is unknown. We hypothesizethat gape coloration is part of a communication system wherenestlings reveal their condition to attending parents, whichmay thus base their decisions on reliable signals of offspringreproductive value. We analyze the effects of brood size manipulation,injection with an immunogen and food deprivation, on gape coloration,morphology, and T-cellmediated immunocompetence of nestlingbarn swallows (Hirundo rustica). For each gape we measured threecomponents of coloration (hue, saturation, and brightness) andobtained an overall color score by principal component analysis.Enlargement of brood size and injection with an antigen resultedin less red and less saturated and brighter gape color. Nestlingsin enlarged broods had smaller body mass and T-cellmediatedimmunocompetence compared to those in reduced broods. A positivecovariation existed between redness and saturation of gape colorand T-cellmediated immunocompetence. Gape color siblingsraised in different nests did not depend on parentage. Thus,condition-dependent gape coloration can reveal different componentsof nestling state on which parents may base their adaptive decisionsabout allocation of care to the offspring. 相似文献
993.
Antonio Giordano Paola Cesari Lorena Capparuccia Mario Castellucci Saverio Cinti 《Brain Cell Biology》2003,32(4):345-352
Semaphorins are cell surface and/or soluble signals that exert an inhibitory control on axon guidance. Sema3A, the vertebrate-secreted semaphorin, binds to neuropilin-1, which together with plexins constitutes the functional receptor. To verify whether Sema3A is produced by white adipocytes and, in that case, to detect its targets in white adipose tissue, we studied the cell production and tissue distribution of Sema3A and neuropilin-1 in rat retroperitoneal and epididymal adipose depots. Sema3A and neuropilin-1 were detected in these depots by Western blotting. The immunohistochemical results showed that Sema3A is produced in, and possibly secreted by, smooth muscle cells of arteries and white adipocytes. Accordingly, neuropilin-1 was found on perivascular and parenchymal nerves. Such a pattern of distribution is in line with a role for secreted Sema3A in the growth and plasticity of white adipose tissue nerves. Indeed, after fasting, when white adipocytes are believed to be overstimulated by noradrenaline and rearrangement of the parenchymal nerve supply may occur, adipocytic expression of Sema3A is reduced. Finally, the presence of neuropilin-1 in some white adipocytes raises the interesting possibility that Sema3A also exerts an autocrine-paracrine role on these cells. 相似文献
994.
The effect of different cations on the conformational and morphological properties of the capsular polysaccharide produced by Neisseria meningitidis group A was investigated. Circular dichroism studies showed that the presence of Na+, or Ca2+ ions induced different local conformations of the polysaccharide chain through interactions with the phosphodiester group bridging the saccharide residues in the polymer chain. Atomic force microscopy experiments confirmed that the morphology of the polysaccharide chains was different depending on the nature of the counterion. Ammonium ions were associated with the presence of single polymer chains in an elongated conformation, whereas sodium ions favored the folding of the chains into a globular conformation. The addition of calcium ions produced the aggregation of a limited number of globular polysaccharide chains to form a ‘toroidal-like’ structure. 相似文献
995.
Ornella Spadoni Alessio Crestini Paola Piscopo Lorenzo Malvezzi-Campeggi Irene Carunchio Massimo Pieri Cristina Zona Annamaria Confaloni 《Cellular and molecular neurobiology》2009,29(5):635-641
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease defined by motor neuron loss. Transgenic mouse
model (Tg SOD1G93A) shows pathological features that closely mimic those seen in ALS patients. An hypothetic link between
AD and ALS was suggested by finding an higher amount of amyloid precursor protein (APP) in the spinal cord anterior horn neurons,
and of Aβ peptides in ALS patients skin. In this work, we have investigated the expression of some genes involved in Alzheimer’s
disease, as APP, β- and γ-secretase, in an animal model of ALS, to understand some possible common molecular mechanisms between
these two pathologies. For gene expression analysis, we carried out a quantitative RT-PCR in ALS mice and in transgenic mice
over-expressing human wild-type SOD1 (Tg hSOD1). We found that APP and BACE1 mRNA levels were increased 1.5-fold in cortical
cells of Tg SOD1G93A mice respect to Tg hSOD1, whereas the expression of γ-secretase genes, as PSEN1, PSEN2, Nicastrin, and
APH1a, showed no statistical differences between wild-type and ALS mice. Biochemical analysis carried out by immunostaining
and western blotting, did not show any significant modulation of the protein expression compared to the genes, suggesting
the existence of post-translational mechanisms that modify protein levels. 相似文献
996.
Modified peptides in anti-cancer vaccines: are we eventually improving anti-tumour immunity? 总被引:1,自引:0,他引:1
Iero M Filipazzi P Castelli C Belli F Valdagni R Parmiani G Patuzzo R Santinami M Rivoltini L 《Cancer immunology, immunotherapy : CII》2009,58(7):1159-1167
The discovery of tumour antigens recognized by T cells and the features of immune responses directed against them has paved
the way to a multitude of clinical studies aimed at boosting anti-tumour T cell immunity as a therapeutic tool for cancer
patients. One of the different strategies explored to ameliorate the immunogenicity of tumour antigens in vaccine protocols
is represented by the use of optimized peptides or altered peptide ligands, whose amino acid sequence has been modified for
improving HLA binding or TCR interaction with respect to native epitopes. However, despite the promising results achieved
with preclinical studies, the clinical efficacy of this approach has not yet met the expectations. Although multiple reasons
could explain the relative failure of altered peptide ligands as more effective cancer vaccines, the possibility that T cells
primed by modified tumour peptides might may be unable to effectively cross-recognize tumour cells has not been sufficiently
addressed. Indeed, the introduction of conservative amino acid substitutions may still produce diverse and unpredictable changes
in the HLA/peptide interface, with consequent modifications of the TCR repertoire that can interact with the complex. This
could lead to the expansion of a broad array of T cells whose TCRs may not necessarily react with equivalent affinity with
the original antigenic epitope. Considering the results presently achieved with this vaccine approach, and the emerging availability
of alternative strategies for boosting anti-tumour immunity, the use of modified tumour peptides could be reconsidered.
This article is a symposium paper from the conference “Immunotherapy—From Basic Research to Clinical Applications”, Symposium
of the Collaborative Research Center (SFB) 685, held in Tübingen, Germany, 6–7 March 2008. 相似文献
997.
Paola Bergamini Antonella Pagnoni Tiziana Franceschetti Roberta Piva 《Journal of inorganic biochemistry》2009,103(6):891-897
The strontium salts Sr(cholate)2, (Compound 1), Sr(dehydrocholate)2, (Compound 2) and Sr3(3-dehydrocholanoyliden-l-tartrate)2, (Compound 3) have been prepared and characterized. The potential anti-osteoporotic activity of these compounds was tested on human primary osteoblasts (hOBs) and human primary osteoclasts (hOCs) in comparison with the bioactivity of strontium ranelate, previously registered as drug in the treatment of post-menopausal osteoporosis. Our results led to the hypothesis that the tested compounds, particularly Compound 2, may have requirements for modulating skeletal tissue regeneration or at least down regulating the loss of bone mass. In fact, all tested compounds have been shown to induce maturation in human primary osteoblasts (hOBs) and apoptosis of human primary osteoclasts (hOCs) at the same time. 相似文献
998.
In Southern Italy, an endemic monotypic genus belonging to family Apiaceae occurs: Petagnaea (P. gussonei), relict of Tertiary flora, belonging to subfamily Saniculoideae. At present, P. gussonei is an endangered species and is included in various lists of species deserving special protection. The genus belongs to scapose hemicryptophytes and shares a sciaphilous habitat (hygrophilous woodland). This study is aimed at doing a complete contribution about the evolutionary history of Petagnaea, using molecular markers as plastidial DNA (cpDNA), nuclear ribosomal DNA (rDNA) and data present in literature. We used nucleotide sequences from four regions of the chloroplast genome (rps16 intron, trnL(UAA) intron, atpB-rbcL intergenic spacer, and partial matK gene) to investigate possible haplotypes in Petagnaea populations. To have an idea of the molecular relationships of all populations of P. gussonei, the internal transcribed spacer (ITS) sequences, already employed in recent studies, were obtained for 18 populations. These sequences in combination with other Saniculoideae ITS sequences available from GenBank have been used for a further phylogenetic analysis. The results agree with the current classification of Saniculoideae in placing P. gussonei in tribe Saniculeae, since P. gussonei is in basal position to Sanicula. According to intraspecific chloroplast DNA diversity, no different haplotypes were detected. In addition to molecular data, morphology, cytology, phytochemistry and conservation status have been considered in the discussion. 相似文献
999.
Paola Venditti Angela Bari Lisa Di Stefano Sergio Di Meo 《Free radical biology & medicine》2009,46(3):360-366
We investigated whether swim training modifies the effect of T3-induced hyperthyroidism on metabolism and oxidative damage in rat muscle. Respiratory capacities, oxidative damage, levels of antioxidants, and susceptibility to oxidative challenge of homogenates were determined. Mitochondrial respiratory capacities, H2O2 release rates, and oxidative damage were also evaluated. T3-treated rats exhibited increases in muscle respiratory capacity, which were associated with enhancements in mitochondrial respiratory capacity and tissue mitochondrial protein content in sedentary and trained animals, respectively. Hormonal treatment induced muscle oxidative damage and GSH depletion. Both effects were reduced by training, which also attenuated tissue susceptibility to oxidative challenge. The changes in single antioxidant levels were slightly related to oxidative damage extent, but the examination of parameters affecting the susceptibility to oxidants indicated that training was associated with greater effectiveness of the muscle antioxidant system. Training also attenuated T3-induced increases in H2O2 production and, therefore, oxidative damage of mitochondria by lowering their content of autoxidizable electron carriers. The above results suggest that moderate training is able to reduce hyperthyroid state-linked tissue oxidative damage, increasing antioxidant protection and decreasing the ROS flow from the mitochondria to the cytoplasmic compartment. 相似文献
1000.
Donati C Cencetti F De Palma C Rapizzi E Brunelli S Cossu G Clementi E Bruni P 《Cellular signalling》2009,21(2):228-236
Mesoangioblasts are vessel-derived progenitor cells that can be induced to differentiate into different cell types of the mesoderm such as muscle and bone. Here we examined the role of transforming growth factor-beta (TGFbeta), a pleiotropic cytokine that plays a major role in development and specifically induces smooth muscle differentiation of mesoangioblasts, in the regulation of death and survival of these cells. TGFbeta exerts a marked anti-apoptotic action in mesoangioblasts with a mechanism involving regulation of sphingosine kinase 1 (SphK1), one of the isoforms responsible for S1P formation. Treatment with the cytokine efficaciously protected mesoangioblasts from apoptosis induced by serum starvation or staurosporine treatment assessed by various means such as activation of caspase-3, determination of cytoplasmic histone-associated-DNA-fragments and PE-AnnexinV staining. The protective action of TGFbeta from staurosporine-induced apoptosis was strongly reduced when the SphK activity was inhibited by drugs, when SphK1 but not SphK2 was downregulated by specific siRNA and when a SphK1 dominant negative mutant was overexpressed. Staurosporine treatment induced down-regulation of both SphK isoforms and TGFbeta rescued SphK1 but not SphK2 expression. Interestingly, TGFbeta strongly enhanced SphK activity during staurosporine-induced cell death. Both TGFbeta-induced SphK1 up-regulation and TGFbeta anti-apoptotic action were found to be dependent on p42/44 MAPK activation. 相似文献