全文获取类型
收费全文 | 5783篇 |
免费 | 447篇 |
出版年
2023年 | 32篇 |
2022年 | 59篇 |
2021年 | 160篇 |
2020年 | 76篇 |
2019年 | 130篇 |
2018年 | 155篇 |
2017年 | 139篇 |
2016年 | 216篇 |
2015年 | 326篇 |
2014年 | 356篇 |
2013年 | 468篇 |
2012年 | 543篇 |
2011年 | 525篇 |
2010年 | 323篇 |
2009年 | 263篇 |
2008年 | 355篇 |
2007年 | 367篇 |
2006年 | 330篇 |
2005年 | 262篇 |
2004年 | 258篇 |
2003年 | 230篇 |
2002年 | 207篇 |
2001年 | 41篇 |
2000年 | 28篇 |
1999年 | 35篇 |
1998年 | 44篇 |
1997年 | 22篇 |
1996年 | 32篇 |
1995年 | 27篇 |
1994年 | 17篇 |
1993年 | 14篇 |
1992年 | 35篇 |
1991年 | 20篇 |
1990年 | 17篇 |
1989年 | 10篇 |
1988年 | 14篇 |
1987年 | 14篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 2篇 |
排序方式: 共有6230条查询结果,搜索用时 171 毫秒
981.
982.
Francesca Gherardi Sandro Bertolino Marco Bodon Sandra Casellato Simone Cianfanelli Marco Ferraguti Elisabetta Lori Graziella Mura Annamaria Nocita Nicoletta Riccardi Giampaolo Rossetti Emilia Rota Riccardo Scalera Sergio Zerunian Elena Tricarico 《Biological invasions》2008,10(4):435-454
The paper provides a list of the non-indigenous animal species occurring today in Italian inland waters. Xenodiversity was
found to amount to 112 species (64 invertebrates and 48 vertebrates), which contribute for about 2% to the inland-water fauna
in Italy. Northern and central regions are most affected, and Asia, North America, and the rest of Europe are the main donor
continents. The large majority of non-indigenous species entered Italy as a direct or indirect effect of human intervention.
A difference between invertebrates and vertebrates was found for their mode of arrival (unintentional for invertebrates and
intentional for vertebrates). Accidental transport, in association with both fish (for aquaculture or stock enhancement) and
crops, has been the main vector of invertebrate introductions, whereas vertebrates were mostly released for stocking purposes.
Overall stock enhancement (47.92%) and culture (37.5%) prevailed over the other pathways. Seventeen and 7 species of our list
are included among the 100 worst invasive species of Europe (DAISIE) and of the world (IUCN), respectively. For some (but
not all) non-indigenous species recorded in Italy the multilevel impact exerted on the recipient communities and ecosystems
is known, even if rarely quantified, but knowledge on their chronic impact is still missing. Additional research is needed
to provide criteria for prioritizing intervention against well established invaders and identify which new potential invader
should be targeted as “unwanted”. 相似文献
983.
Raciti D Reggiani L Geffers L Jiang Q Bacchion F Subrizi AE Clements D Tindal C Davidson DR Kaissling B Brändli AW 《Genome biology》2008,9(5):R84-21
Background
The pronephros, the simplest form of a vertebrate excretory organ, has recently become an important model of vertebrate kidney organogenesis. Here, we elucidated the nephron organization of the Xenopus pronephros and determined the similarities in segmentation with the metanephros, the adult kidney of mammals.Results
We performed large-scale gene expression mapping of terminal differentiation markers to identify gene expression patterns that define distinct domains of the pronephric kidney. We analyzed the expression of over 240 genes, which included members of the solute carrier, claudin, and aquaporin gene families, as well as selected ion channels. The obtained expression patterns were deposited in the searchable European Renal Genome Project Xenopus Gene Expression Database. We found that 112 genes exhibited highly regionalized expression patterns that were adequate to define the segmental organization of the pronephric nephron. Eight functionally distinct domains were discovered that shared significant analogies in gene expression with the mammalian metanephric nephron. We therefore propose a new nomenclature, which is in line with the mammalian one. The Xenopus pronephric nephron is composed of four basic domains: proximal tubule, intermediate tubule, distal tubule, and connecting tubule. Each tubule may be further subdivided into distinct segments. Finally, we also provide compelling evidence that the expression of key genes underlying inherited renal diseases in humans has been evolutionarily conserved down to the level of the pronephric kidney.Conclusion
The present study validates the Xenopus pronephros as a genuine model that may be used to elucidate the molecular basis of nephron segmentation and human renal disease. 相似文献984.
Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Genome biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cardone MF Jiang Z D'Addabbo P Archidiacono N Rocchi M Eichler EE Ventura M 《Genome biology》2008,9(2):R28
Background
Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. 相似文献985.
The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression 总被引:2,自引:0,他引:2
Org T Chignola F Hetényi C Gaetani M Rebane A Liiv I Maran U Mollica L Bottomley MJ Musco G Peterson P 《EMBO reports》2008,9(4):370-376
Mutations in the gene autoimmune regulator (AIRE) cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed in thymic medullary epithelial cells, where it promotes the expression of tissue-restricted antigens. By the combined use of biochemical and biophysical methods, we show that AIRE selectively interacts with histone H3 through its first plant homeodomain (PHD) finger (AIRE-PHD1) and preferentially binds to non-methylated H3K4 (H3K4me0). Accordingly, in vivo AIRE binds to and activates promoters containing low levels of H3K4me3 in human embryonic kidney 293 cells. We conclude that AIRE-PHD1 is an important member of a newly identified class of PHD fingers that specifically recognize H3K4me0, thus providing a new link between the status of histone modifications and the regulation of tissue-restricted antigen expression in thymus. 相似文献
986.
Beretta L Cossu M Marchini M Cappiello F Artoni A Motta G Scorza R 《Arthritis research & therapy》2008,10(5):R103-7
Introduction
Platelet aggregation may contribute to the pathogenesis of systemic sclerosis: following activation, platelets release significant amounts of serotonin – which promotes vasoconstriction and fibrosis, and further enhances aggregation. The C+1354T polymorphism in the exonic region of the serotonin 2A receptor gene determining the His452Tyr substitution was associated with blunted intracellular responses after serotonin stimulation, and may have a role in susceptibility to scleroderma.Methods
One hundred and fifteen consecutive systemic sclerosis patients and 140 well-matched healthy control individuals were genotyped by sequence-specific primer-PCR for the His452Tyr substitution of the serotonin 2A receptor gene, and associations were sought with scleroderma and its main clinical features. The functional relevance of the His452Tyr substitution was also assessed by evaluating the aggregation of platelet-rich plasma from His452/His452 and His452/Tyr452 healthy individuals after stimulation with adenosine diphosphate ± serotonin.Results
The T allele of the C+1354T polymorphism was underrepresented in scleroderma patients compared with control individuals (5.2% versus 12.4%, P < 0.001, chi-square test and 1,000-fold permutation test) and its carriage reduced the risk for systemic sclerosis (odds ratio = 0.39, 95% confidence interval = 0.19 to 0.85, P < 0.01). Platelets from His452/Tyr452 healthy subjects more weakly responded to serotonin stimulation compared with platelets from His452/His452 individuals (3.2 ± 2.6-fold versus 9.6 ± 8.6-fold increase in aggregation, P = 0.017 by Kolmogorov–Smirnov test and P = 0.003 after correction for baseline adenosine diphosphate-induced aggregation values).Conclusion
The His452Tyr substitution may influence susceptibility to systemic sclerosis by altering platelet aggregation in response to serotonin. 相似文献987.
Magni F Chinello C Raimondo F Mocarelli P Kienle MG Pitto M 《Expert review of proteomics》2008,5(1):29-43
Aquaporin (AQP)1 belongs to a ubiquitous family of water channel proteins characterized by sequence similarity and the presence of two NPA (Asp-Pro-Ala) motifs existing in almost all organs and tissues. Currently, 13 human AQPs are known and they are divided into two subgroups according to their ability to transport only water molecules, such as AQP1, or also glycerol and other small solutes. The genomic, structural and functional aspects of AQP1 are briefly described. An in-depth discussion is devoted to proteomic approaches that are useful for identifying and characterizing AQP1, mainly through electrophoretic techniques combined with different extraction procedures followed by mass spectrometry analysis. Moreover, the relevance of AQP1 in human diseases is also explained. Its role in human tumors and, in particular, those of the kidney (e.g., clear cell renal carcinoma) is discussed. 相似文献
988.
Buttarelli FR Pellicano C Pontieri FE 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2008,147(4):399-408
Planarians are the simplest animals to exhibit a body plan common to all vertebrates and many invertebrates, characterized by bilateral rather than radial symmetry, dorsal and ventral surfaces, and a rostrocaudal axis with a head and a tail, including specialized sense organs and an aggregate of nerve cells in the head. Neurons in planarian more closely resemble those of vertebrates than those of advanced invertebrates, exhibiting typical vertebrate features of multipolar shape, dendritic spines with synaptic boutons, a single axon, expression of vertebrate-like neural proteins, and relatively low spontaneously generated electrical activity. Here we report the most relevant contribution to the knowledge of the neuropharmacology of planarians, with particular reference to the behavioral consequences of the exposure to drugs acting on neural transmission. Neurochemical and histochemical data indicate the presence of several neurotransmitter-receptor systems in planarians. Moreover, a variety of experimental studies characterized specific behavioral patterns of these animals following the exposure to drugs acting on neural transmission. There is also evidence of the interactions between discrete neurotransmitter-receptor systems in modulating behavior in planarians. Finally, the model has proved efficacy for investigating the neurotoxicology of the dopamine neurons, and for the initial screening of the neuroprotective potential of drugs. In conclusion, these findings indicate that interactions between discrete neurotransmitter-receptor systems occur very early along phylogeny, although they may have evolved from very fundamental behaviors, such as motor activity in planarian, to more complex and integrated functions in vertebrates. 相似文献
989.
Lovato L Cianti R Gini B Marconi S Bianchi L Armini A Anghileri E Locatelli F Paoletti F Franciotta D Bini L Bonetti B 《Molecular & cellular proteomics : MCP》2008,7(12):2337-2349
The presence of autoantibodies in multiple sclerosis (MuS) is well known, but their target antigens have not been clearly identified. In the present study, IgG autoreactivity to neural antigens of normal human white matter separated by bidimensional electrophoresis was assessed in serum and cerebrospinal fluid of 18 MuS and 20 control patients. Broad IgG autoreactivity was detected by two-dimensional immunoblotting in all cases to neural antigens, most of which were identified by mass spectrometry. The comparative analysis of MuS and non-MuS reactive spots showed that a restricted number of neural protein isoforms were specifically recognized by MuS IgG. Almost all MuS patients had cerebrospinal fluid IgG directed to isoforms of one of the oligodendroglial molecules, transketolase, 2',3'-cyclic-nucleotide 3'-phosphodiesterase type I, collapsin response mediator protein 2, and tubulin beta 4. Interestingly 50% of MuS IgG recognized transketolase, which was mostly localized on oligodendrocytes in human white matter from normal and MuS samples. IgG autoreactivity to cytoskeletal proteins (radixin, sirtuin 2, and actin-interacting protein 1) was prevalent in secondary progressive MuS patients. Among the proteins recognized by serum IgG, almost all MuS patients specifically recognized a restricted number of neuronal/cytoskeletal proteins, whereas 2',3'-cyclic-nucleotide 3'-phosphodiesterase type I was the oligodendroglial antigen most frequently recognized (44%) by MuS seric IgG. Our immunomics approach shed new light on the autoimmune repertoire present in MuS patients revealing novel oligodendroglial and/or neuronal putative autoantigens with potential important pathogenic and diagnostic implications. 相似文献
990.
We devised a short-term culture system allowing us to define novel characteristics of programmed cell death (PCD) of fetal oocytes and to underscore new aspects of this process. Mouse fetal oocytes cultured in conditions allowing meiotic progression underwent apoptotic degeneration as revealed by TUNEL staining, DNA ladder, Annexin V binding, PARP cleavage and, usually, caspase activation. TEM observations show, however, recurrent atypical apoptotic morphologies characterized by the absence of chromatin margination and nuclear fragmentation; oocytes with autophagic and necrotic features are also observed. Moreover, under the fluorescence microscope a subpopulation of TUNEL(+) oocytes appear morphologically healthy and do not show detectable caspase activity. Finally, caspase inhibitors are able to slow down, but not to abolish, oocyte cell death, whereas calpain inhibitor I significantly reduces the number of TUNEL(+) oocytes after 4 days of culture, and rapamycin (mTOR inhibitor) increases such numbers both at day 3 and 4. These observations together with results showing expression in cultured oocytes undergoing cell death of apoptosis inducing factor and Beclin 1, two important players of caspase independent and autophagic cell death, respectively, demonstrate that fetal oocytes possess and are able to activate several players of various forms of cell death. However, causal correlation among different cell death pathways in such oocytes remains to be determined and stimuli causing the activation of these pathways in vitro and in vivo also clarified. 相似文献