全文获取类型
收费全文 | 3070篇 |
免费 | 217篇 |
专业分类
3287篇 |
出版年
2023年 | 6篇 |
2022年 | 21篇 |
2021年 | 59篇 |
2020年 | 35篇 |
2019年 | 60篇 |
2018年 | 70篇 |
2017年 | 58篇 |
2016年 | 87篇 |
2015年 | 137篇 |
2014年 | 174篇 |
2013年 | 235篇 |
2012年 | 262篇 |
2011年 | 258篇 |
2010年 | 170篇 |
2009年 | 129篇 |
2008年 | 189篇 |
2007年 | 200篇 |
2006年 | 187篇 |
2005年 | 162篇 |
2004年 | 159篇 |
2003年 | 136篇 |
2002年 | 135篇 |
2001年 | 34篇 |
2000年 | 19篇 |
1999年 | 18篇 |
1998年 | 35篇 |
1997年 | 24篇 |
1996年 | 27篇 |
1995年 | 24篇 |
1994年 | 23篇 |
1993年 | 27篇 |
1992年 | 17篇 |
1991年 | 18篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1978年 | 4篇 |
1976年 | 3篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1969年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有3287条查询结果,搜索用时 15 毫秒
101.
Massimo Dal Monte Maurizio Cammalleri Valeria Pecci Monica Carmosino Giuseppe Procino Alessandro Pini Mario De Rosa Vincenzo Pavone Maria Svelto Paola Bagnoli 《Journal of cellular and molecular medicine》2019,23(2):1034-1049
The urokinase‐type plasminogen activator (uPA) receptor (uPAR) participates to the mechanisms causing renal damage in response to hyperglycaemia. The main function of uPAR in podocytes (as well as soluble uPAR ‐(s)uPAR‐ from circulation) is to regulate podocyte function through αvβ3 integrin/Rac‐1. We addressed the question of whether blocking the uPAR pathway with the small peptide UPARANT, which inhibits uPAR binding to the formyl peptide receptors (FPRs) can improve kidney lesions in a rat model of streptozotocin (STZ)‐induced diabetes. The concentration of systemically administered UPARANT was measured in the plasma, in kidney and liver extracts and UPARANT effects on dysregulated uPAR pathway, αvβ3 integrin/Rac‐1 activity, renal fibrosis and kidney morphology were determined. UPARANT was found to revert STZ‐induced up‐regulation of uPA levels and activity, while uPAR on podocytes and (s)uPAR were unaffected. In glomeruli, UPARANT inhibited FPR2 expression suggesting that the drug may act downstream uPAR, and recovered the increased activity of the αvβ3 integrin/Rac‐1 pathway indicating a major role of uPAR in regulating podocyte function. At the functional level, UPARANT was shown to ameliorate: (a) the standard renal parameters, (b) the vascular permeability, (c) the renal inflammation, (d) the renal fibrosis including dysregulated plasminogen‐plasmin system, extracellular matrix accumulation and glomerular fibrotic areas and (e) morphological alterations of the glomerulus including diseased filtration barrier. These results provide the first demonstration that blocking the uPAR pathway can improve diabetic kidney lesion in the STZ model, thus suggesting the uPA/uPAR system as a promising target for the development of novel uPAR‐targeting approaches. 相似文献
102.
Filippo Maggi Claudia Giuliani Gelsomina Fico Massimo Ricciutelli Massimo Bramucci Luana Quassinti 《Plant biosystems》2019,153(2):325-335
Apium nodiflorum (L.) Lag. (water celery) is an hydrophytic plant forming dense submerged populations occurring along streams and rivers of Europe. In the present work we provided new insights into the phytochemistry and biology of A. nodiflorum. In particular, we studied the chemical profile of essential oil and polar extracts obtained from the flowering aerial parts of water celery growing in central Italy, together with the essential oil biological activities, namely antimicrobial, antioxidant and cytotoxicity on tumour cells. In addition, we correlated the productivity in secondary metabolites to the secreting structures through a detailed micromorphological study. The essential oil was dominated by two main chemotypes, characterized by myristicin and limonene, respectively. The oils showed significant toxicity on tumour cells, as evidenced by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, with IC50 values in the range 3.8–15.9 μg mL?1, together with inhibitory effects on Candida albicans (inhibition zones of 10–11 mm). HPLC-MS analysis showed the caffeoylquinic acids and quercetin-3-O-glucoside as the most abundant phenolic compounds. Ducts and vittae were the principal secretory structures of vegetative (leaves and stems) and reproductive (fruits) parts, respectively, storing mainly essential oil. Results of this work provide scientific evidences for the possible valorization and exploitation of water celery. 相似文献
103.
Domenico Rau Maria L. Murgia Monica Rodriguez Elena Bitocchi Elisa Bellucci Davide Fois Diego Albani Laura Nanni Tania Gioia Debora Santo Luca Marcolungo Massimo Delledonne Giovanna Attene Roberto Papa 《The Plant journal : for cell and molecular biology》2019,97(4):693-714
The complete or partial loss of shattering ability occurred independently during the domestication of several crops. Therefore, the study of this trait can provide an understanding of the link between phenotypic and molecular convergent evolution. The genetic dissection of ‘pod shattering’ in Phaseolus vulgaris is achieved here using a population of introgression lines and next‐generation sequencing techniques. The ‘occurrence’ of the indehiscent phenotype (indehiscent versus dehiscent) depends on a major locus on chromosome 5. Furthermore, at least two additional genes are associated with the ‘level’ of shattering (number of shattering pods per plant: low versus high) and the ‘mode’ of shattering (non‐twisting versus twisting pods), with all of these loci contributing to the phenotype by epistatic interactions. Comparative mapping indicates that the major gene identified on common bean chromosome 5 corresponds to one of the four quantitative trait loci for pod shattering in Vigna unguiculata. None of the loci identified comprised genes that are homologs of the known shattering genes in Glycine max. Therefore, although convergent domestication can be determined by mutations at orthologous loci, this was only partially true for P. vulgaris and V. unguiculata, which are two phylogenetically closely related crop species, and this was not the case for the more distant P. vulgaris and G. max. Conversely, comparative mapping suggests that the convergent evolution of the indehiscent phenotype arose through mutations in different genes from the same underlying gene networks that are involved in secondary cell‐wall biosynthesis and lignin deposition patterning at the pod level. 相似文献
104.
Michela Buccioni Diego Dal Ben Catia Lambertucci Aleix Martí Navia Massimo Ricciutelli Andrea Spinaci Rosaria Volpini Gabriella Marucci 《Bioorganic & medicinal chemistry》2019,27(15):3328-3333
In recent years, special attention has been paid to the A3 adenosine receptor (A3AR) as a possible pharmacological target to treat intestinal inflammation. In this work, it was set up a novel method to quantify the concentration of a promising anti-inflammatory agent inside and outside of intestinal barrier using the everted gut sac technique. The compound chosen for the present study is one of the most potent and selective A3AR agonist reported so far, named AR 170 (N6-methyl-2-phenylethynyl-5′-N-methylcarboxamidoadenosine). In order to evaluate the intestinal absorption of AR 170 the radioligand binding assay in comparison with HPLC-DAD was used. Results showed that the compound is absorbed via passive diffusion by paracellular pathway. The concentrations determined in the serosal (inside the sac) fluid by radioligand binding assay are in good agreement with those obtained through the widely used HPLC/MS protocol, demonstrating the reliability of the method. It is worthwhile to note that the radioligand binding assay allows detecting very low concentrations of analyte, thus offering an excellent tool to measure the intestinal absorption of receptor ligands. Moreover, the AR 170 quantity outside the gut sac and the interaction with A3AR could presuppose good topical anti-inflammatory effects of this compound. 相似文献
105.
Saber Khederzadeh Szilvia Kusza Cui‐Ping Huang Nickolay Markov Massimo Scandura Elmar Babaev Nikica prem Ivan V. Seryodkin Ladislav Paule Ali Esmailizadeh Hai‐Bing Xie Ya‐Ping Zhang 《Ecology and evolution》2019,9(17):9467-9478
The phylogeography of the European wild boar was mainly determined by postglacial recolonization patterns from Mediterranean refugia after the last ice age. Here we present the first analysis of SNP polymorphism within the complete mtDNA genome of West Russian (n = 8), European (n = 64), and North African (n = 5) wild boar. Our analyses provided evidence of unique lineages in the East‐Caucasian (Dagestan) region and in Central Italy. A phylogenetic analysis revealed that these lineages are basal to the other European mtDNA sequences. We also show close connection between the Western Siberian and Eastern European populations. Also, the North African samples were clustered with the Iberian population. Phylogenetic trees and migration modeling revealed a high proximity of Dagestan sequences to those of Central Italy and suggested possible gene flow between Western Asia and Southern Europe which was not directly related to Northern and Central European lineages. Our results support the presence of old maternal lineages in two Southern glacial refugia (i.e., Caucasus and the Italian peninsula), as a legacy of an ancient wave of colonization of Southern Europe from an Eastern origin. 相似文献
106.
Jean-Marc Bielser Jakub Domaradzki Jonathan Souquet Hervé Broly Massimo Morbidelli 《Biotechnology progress》2019,35(3):e2790
Perfusion cell culture, confined traditionally to the production of fragile molecules, is currently gaining broader attention in the biomanufacturing of therapeutic proteins. The development of these processes is made difficult by the limited availability of appropriate scale-down models. This is due to the continuous operation that requires complex control and cell retention capacity. For example, the determination of an optimal perfusion and bleed rate for continuous cell culture is often performed in scale-down bioreactors and requires a substantial amount of time and effort. To increase the experimental throughput and decrease the required workload, a semi-continuous procedure, referred to as the VCDmax (viable cell density) approach, has been developed on the basis of shake tubes (ST) and deepwell plates (96-DWP). Its effectiveness has been demonstrated for 12 different CHO-K1-SV cell lines expressing an IgG1. Further, its reliability has been investigated through proper comparisons with perfusion runs in lab-scale bioreactors. It was found that the volumetric productivity and the CSPRmin (cell specific perfusion rate) determined using the ST and 96-DWP models were successfully (mostly within the experimental error) confirmed in lab-scale bioreactors, which then covered a significant scale-up from the half milliliter to the liter scale. These scale-down models are very useful to design and scale-up optimal bioreactor operating conditions as well as screening for different media and cell lines. 相似文献
107.
Chemoattractant action and molecular signaling pathways of Kit ligand on mouse primordial germ cells
Using a Transwell chamber as migration assay for mouse primordial germ cells (PGCs), we show here that these cells posses directional migration in the absence of somatic cell and defined matrix support and in response to a Kit ligand (KL) gradient or medium conditioned by Aorta/Gonad/Mesonephros and gonadal ridges. Other putative PGC chemoattractants such as SDF1 and TGFbeta did not exert any attractive action on PGCs. The chemoattractant activity of KL and conditioned medium was also evidenced by their ability to stimulate actin reorganization in PGCs. In the aim to identify downstream signaling pathways governing KL chemoattraction on PGCs, we demonstrated that in such cells KL rapidly (5 min) increased autophosphorylation of its receptor c-Kit and caused phosphorylation of the serine-threonine kinase AKT through the action of PI3K. 740Y-P peptide, a direct activator of PI3 kinase, stimulated PGC migration at levels similar to those elicited by KL. LY294002 (a specific inhibitor of PI3K) abolished KL-dependent PGC migration or the chemoattractant activity of the conditioned medium and inhibited AKT phosphorylation; Src kinase inhibitors PP2 and SU6656, caused significant reduction of the KL-dependent PGC migration and AKT phosphorylation, while U0126, a selective inhibitor of the MEK/ERK protein kinase cascade, reduced PGC migration and AKT phosphorylation at lesser extent. SU6656 completely abolished the chemoattractant activity of the conditioned medium. Finally, SB202190 (a p38 inhibitor) and rapamycin (mTOR inhibitor) did not affect PGC migration. In addition, to demonstrate that somatic cells are not essential for PGC motility and directional migration, we evidenced a novel role for KL as PGC chemoattractant and for PI3K/AKT and Src kinase, as players involved in the activation of the PGC migratory machinery and likely important for their directional movement towards the gonadal ridges. 相似文献
108.
XSip1 neuralizing activity involves the co-repressor CtBP and occurs through BMP dependent and independent mechanisms 总被引:2,自引:0,他引:2
109.
A dense single-nucleotide polymorphism-based genetic linkage map of grapevine (Vitis vinifera L.) anchoring Pinot Noir bacterial artificial chromosome contigs 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Troggio M Malacarne G Coppola G Segala C Cartwright DA Pindo M Stefanini M Mank R Moroldo M Morgante M Grando MS Velasco R 《Genetics》2007,176(4):2637-2650
The construction of a dense genetic map for Vitis vinifera and its anchoring to a BAC-based physical map is described: it includes 994 loci mapped onto 19 linkage groups, corresponding to the basic chromosome number of Vitis. Spanning 1245 cM with an average distance of 1.3 cM between adjacent markers, the map was generated from the segregation of 483 single-nucleotide polymorphism (SNP)-based genetic markers, 132 simple sequence repeats (SSRs), and 379 AFLP markers in a mapping population of 94 F(1) individuals derived from a V. vinifera cross of the cultivars Syrah and Pinot Noir. Of these markers, 623 were anchored to 367 contigs that are included in a physical map produced from the same clone of Pinot Noir and covering 352 Mbp. On the basis of contigs containing two or more genetically mapped markers, region-dependent estimations of physical and recombinational distances are presented. The markers used in this study include 118 SSRs common to an integrated map derived from five segregating populations of V. vinifera. The positions of these SSR markers in the two maps are conserved across all Vitis linkage groups. The addition of SNP-based markers introduces polymorphisms that are easy to database, are useful for evolutionary studies, and significantly increase the density of the map. The map provides the most comprehensive view of the Vitis genome reported to date and will be relevant for future studies on structural and functional genomics and genetic improvement. 相似文献
110.