全文获取类型
收费全文 | 426篇 |
免费 | 12篇 |
国内免费 | 7篇 |
专业分类
445篇 |
出版年
2023年 | 4篇 |
2022年 | 8篇 |
2021年 | 4篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 11篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 6篇 |
2014年 | 17篇 |
2013年 | 22篇 |
2012年 | 14篇 |
2011年 | 19篇 |
2010年 | 7篇 |
2009年 | 10篇 |
2008年 | 9篇 |
2007年 | 22篇 |
2006年 | 10篇 |
2005年 | 9篇 |
2004年 | 12篇 |
2003年 | 12篇 |
2002年 | 16篇 |
2001年 | 7篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 9篇 |
1997年 | 10篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 9篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 12篇 |
1989年 | 13篇 |
1988年 | 12篇 |
1987年 | 8篇 |
1986年 | 16篇 |
1985年 | 4篇 |
1984年 | 17篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 9篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1973年 | 3篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有445条查询结果,搜索用时 15 毫秒
51.
Robert A. Fenton Wing‐Kee Lee Frank Thévenod Craig P. Smith 《Journal of cellular and molecular medicine》2011,15(2):209-219
Ferroportin 1 (FPN1) is an iron export protein expressed in liver and duodenum, as well as in reticuloendothelial macrophages. Previously, we have shown that divalent metal transporter 1 (DMT1) is expressed in late endosomes and lysosomes of the kidney proximal tubule (PT), the nephron segment responsible for the majority of solute reabsorption. We suggested that following receptor mediated endocytosis of transferrin filtered by the glomerulus, DMT1 exports iron liberated from transferrin into the cytosol. FPN1 is also expressed in the kidney yet its role remains obscure. As a first step towards determining the role of renal FPN1, we localized FPN1 in the PT. FPN1 was found to be located in association with the basolateral PT membrane and within the cytosolic compartment. FPN1 was not expressed on the apical brush‐border membrane of PT cells. These data support a role for FPN1 in vectorial export of iron out of PT cells. Furthermore, under conditions of iron loading of cultured PT cells, FPN1 was trafficked to the plasma membrane suggesting a coordinated cellular response to export excess iron and limit cellular iron concentrations. 相似文献
52.
Terada N Ohno N Yamakawa H Ohara O Liao X Baba T Ohno S 《Histochemistry and cell biology》2005,124(3-4):303-311
Protein 4.1 families have recently been established as potential organizers of an adherens system. In the adult mouse testis,
protein 4.1G (4.1G) localized as a line pattern in both basal and adluminal compartments of the seminiferous tubules, attaching
regions of germ cells and Sertoli cells. By double staining for 4.1G and F-actin, their localizations were shown to be different,
indicating that 4.1G was localized in a region other than the basal and apical ectoplasmic specializations, which formed the
Sertoli–Sertoli cell junction and Sertoli–spermatid junction, respectively. By electron microscopy, immunoreactive products
were seen exclusively on the cell membranes of Sertoli cells, attaching to the various differentiating germ cells. The immunolocalization
of cadherin was identical to that of 4.1G, supporting the idea that 4.1G may be functionally interconnected with adhesion
molecules. In an experimental mouse model of cadmium treatment, in which tight and adherens junctions of seminiferous tubules
were disrupted, the 4.1G immunostaining in the seminiferous tubules was dramatically decreased. These results indicate that
4.1G may have a basic adhesive function between Sertoli cells and germ cells from the side of Sertoli cells. 相似文献
53.
Cao Y Baig MR Hamm LL Wu K Simon EE 《Biochemical and biophysical research communications》2005,328(2):560-566
Migration of human proximal tubule cells (HKC-5) was stimulated by epidermal growth factor (EGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1). Integrin signaling via phosphorylation of focal adhesion kinase (FAK) appears to play a central role in cell migration. Once stimulated, FAK undergoes autophosphorylation at tyrosine (Y) 397, followed by phosphorylation of several sites including Y576/Y577 which increases FAK's kinase activity, as well as at Y407, Y861, and Y925. EGF, HGF, and IGF-1 stimulate FAK phosphorylation in various cells. We showed that endothelin stimulated phosphorylation of Y397 in fibroblasts but not HKC-5 cells. After EGF stimulation, HKC-5 cells showed no change in tyrosine phosphorylation at FAK Y397, 407, 576, 861, or 925. Similarly, HGF and IGF-1 did not stimulate the phosphorylation of FAK Y397 in HKC-5 cells. Further, after inhibition of FAK expression by siRNA, cell migration was similar to cells treated with non-target siRNA and responded to EGF with increased migration. Thus, in proximal tubule cells, stimulation of cell migration by growth factors was independent of augmented FAK tyrosine phosphorylation. 相似文献
54.
The organic anion salicylate is a plant secondary metabolite that can protect plants against herbivores. Transport of salicylate across the basolateral membrane of the Malpighian tubules of Drosophila melanogaster was studied using a radioisotope tracer technique. The uptake of [(14)C]salicylate by the Malpighian tubules was active, saturable and Na(+)-dependent; the maximum uptake rate (J(max)) and the half saturation concentration (K(t)) were 12.6 pmoltubule(-1)min(-1) and 30.7micromoll(-1), respectively. In contrast to organic anion transport by vertebrate renal tissues, salicylate uptake was not trans-stimulated by glutarate (0.01-1.0 mmoll(-1)) or cis-inhibited by high concentrations (5 mmoll(-1)) of various alpha-keto acids (glutaric acid, alpha-ketoglutaric acid, succinic acid, and citric acid). Changes in basolateral membrane potential or physiologically relevant changes in bathing saline pH did not affect the rate of [(14)C]salicylate uptake. Ring-structure monocarboxylic acids (benzoic acid, nicotinic acid, gentisic acid, unlabelled salicylic acid, alpha-cyano-4-hydroxycinnamic acid, probenecid, fluorescein, and P-aminohippuric acid) strongly inhibited [(14)C]salicylate uptake rate. In contrast, short-chain monocarboxylic acids had little (butyric acid) or no effect (lactic acid, pyruvic acid, and propionic acid). Our results suggest that salicylate uptake across the basolateral membrane of D. melanogaster Malpighian tubules is mediated by a non-electrogenic, alpha-cyano-4-hydroxycinnamic acid-sensitive, Na(+):salicylate cotransport system. 相似文献
55.
Woost PG Kolb RJ Finesilver M Mackraj I Imboden H Coffman TM Hopfer U 《In vitro cellular & developmental biology. Animal》2006,42(7):189-200
In the proximal convoluted tubule (PCT) angiotensin II (Ang II) modulates fluid and electrolyte transport through at least two pharmacologically distinct receptor subtypes: AT(1) and AT(2). Development of cell lines that lack these receptors are potentially useful models to probe the complex cellular details of Ang II regulation. To this end, angiotensin receptor- deficient mice were bred with an Immortomouse(R), which harbors a thermolabile SV40 large-T antigen (Tag). S1 PCT segments from kidneys of F(2) mice were microdissected, placed in culture, and maintained under conditions that enhanced cell growth, i.e., promoted Tag expression and thermostability. Three different types of angiotensin receptor-deficient cell lines, (AT(1A) [-/-], Tag [+/-]), (AT(1B) [-/-], Tag [+/-]), and (AT(1A) [-/-], AT(1B) [-/-], Tag [+/+]), as well as wild type cell lines were generated. Screening and characterization, which were conducted under culture conditions that promoted cellular differentiation, included: measurements of transepithelial transport, such as basal monolayer short-circuit current (Isc; -3 to 3 microA/cm2), basal monolayer conductance (G, 2 to 10 mS/cm2), Na3(+)-phosphate cotransport (DeltaIsc of 2 to 3 microA/cm(2) at 1 mM), and Na(3)(+)-succinate cotransport (DeltaIsc of 1 to 9 microA/cm(2) at 2 mM). Morphology of cell monolayers showed an extensive brush border, well-defined tight junctions, and primary cilia. Receptor functionality was assessed by Ang II-stimulated beta-arrestin 2 translocation and showed an Ang II-mediated response in wild type but not (AT(1A) [-/ -], AT(1B) [-/-]) cells. Cell lines were amplified, yielding a virtually unlimited supply of highly differentiated, transport-competent, angiotensin receptor-deficient PCT cell lines. 相似文献
56.
Aguirre-Planter E Jaramillo-Correa JP Gómez-Acevedo S Khasa DP Bousquet J Eguiarte LE 《Molecular phylogenetics and evolution》2012,62(1):263-274
The genus Abies is distributed discontinuously in the temperate and subtropical montane forests of the northern hemisphere. In Mesoamerica (Mexico and northern Central America), modern firs originated from the divergence of isolated mountain populations of migrating North American taxa. However, the number of ancestral species, migratory waves and diversification speed of these taxa is unknown. Here, variation in repetitive (Pt30204, Pt63718, and Pt71936) and non-repetitive (rbcL, rps18-rpl20 and trnL-trnF) regions of the chloroplast genome was used to reconstruct the phylogenetic relationships of the Mesoamerican Abies in a genus-wide context. These phylogenies and two fossil-calibrated scenarios were further employed to estimate divergence dates and diversification rates within the genus, and to test the hypothesis that, as in many angiosperms, conifers may exhibit accelerated speciation rates in the subtropics. All phylogenies showed five main clusters that mostly agreed with the currently recognized sections of Abies and with the geographic distribution of species. The Mesoamerican taxa formed a single group with species from southwestern North America of sections Oiamel and Grandis. However, populations of the same species were not monophyletic within this group. Divergence of this whole group dated back to the late Paleocene and the early Miocene depending on the calibration used, which translated in very low diversification rates (r0.0 = 0.026-0.054, r0.9 = 0.009-0.019 sp/Ma). Such low rates were a constant along the entire genus, including both the subtropical and temperate taxa. An extended phylogeographic analysis on the Mesoamerican clade indicated that Abies flinckii and A. concolor were the most divergent taxa, while the remaining species (A. durangensis, A. guatemalensis, A. hickelii, A. religiosa and A. vejari) formed a single group. Altogether, these results show that divergence of Mesoamerican firs coincides with a model of environmental stasis and decreased extinction rate, being probably prompted by a series of range expansions and isolation-by-distance. 相似文献
57.
Bone remodelling is the process that maintains bone structure and strength through adaptation of bone tissue mechanical properties
to applied loads. Bone can be modelled as a porous deformable material whose pores are filled with cells, organic material
and interstitial fluid. Fluid flow is believed to play a role in the mechanotransduction of signals for bone remodelling.
In this work, an osteon, the elementary unit of cortical bone, is idealized as a hollow cylinder made of a deformable porous
matrix saturated with an interstitial fluid. We use Biot’s poroelasticity theory to model the mechanical behaviour of bone
tissue taking into account transverse isotropic mechanical properties. A finite element poroelastic model is developed in
the COMSOL Multiphysics software. Elasticity equations and Darcy’s law are implemented in this software; they are coupled
through the introduction of an interaction term to obtain poroelasticity equations. Using numerical simulations, the investigation
of the effect of spatial gradients of permeability or Poisson’s ratio is performed. Results are discussed for their implication
on fluid flow in osteons: (i) a permeability gradient affects more the fluid pressure than the velocity profile; (ii) focusing
on the fluid flow, the key element of loading is the strain rate; (iii) a Poisson’s ratio gradient affects both fluid pressure
and fluid velocity. The influence of textural and mechanical properties of bone on mechanotransduction signals for bone remodelling
is also discussed. 相似文献
58.
Katavetin P Inagi R Miyata T Tanaka T Sassa R Ingelfinger JR Fujita T Nangaku M 《Biochemical and biophysical research communications》2008,367(2):305-310
Reduction of vascular endothelial growth factor (VEGF) expression plays a crucial role in chronic kidney disease (CKD). In order to clarify a cause of VEGF suppression in CKD, we examined an interaction between proteinuria and VEGF. Rat proximal tubular cells were subjected to hypoxia with or without albumin to mimic proteinuric conditions, and VEGF expression was assessed by real-time quantitative PCR and enzyme-linked immunosorbent assays. Albumin significantly reduced VEGF expression under hypoxia. Luciferase activity controlled by hypoxia-responsive element (HRE) was suppressed by albumin, demonstrating suppression of the hypoxia-inducible factor (HIF)/HRE pathway. Studies utilizing a proteasome inhibitor and a prolyl hydroxylase inhibitor showed that mechanisms of HIF/HRE pathway suppression by albumin load did not involve degradation of HIF protein levels. Further, albumin did not change HIF mRNA levels. Our data, for the first time, suggest a clear ‘link’ between proteinuria and hypoxia, the two principal pathogenic factors for CKD progression. 相似文献
59.
60.
Summary Spermatogenesis occurs within the testis of adult males by a complex and very well organized process. Breakthroughs in techniques such as cryopreservation and culture of spermatogenic cells and the maturation of these cells in exogenous testes after transplantation renewed the interest in this process. Transplantation of spermatogenic cells from a donor to a recipient animal needs a preparatory step that consists in the elimination of the endogenous population of spermatogenic cells. The most common method used to empty the seminiferous tubules is the treatment with busulfan (1,4-butanediol dimethanesulfonate). Busulfan partially eliminates stem cells because of its alkylating nature, but a residual component of stem cells survives the treatment and competes in the regeneration of the testis with transplanted cells. Estradiol has also been used as an agent that causes a delay in the process of spermatogenesis by altering its hormonal stimulation, although it does not affect the spermatogonia population. Therefore, we have tested different treatments with busulfan, estradiol benzoate, and also an agonist of the chorionic gonadotrophin-releasing hormone, leuprolide acetate, for the inhibition of endogenous spermatogenesis. We have found that a combination of estradiol, busulfan, and leuprolide can destroy the population of endogenous spermatogenic cells without altering Sertoli cells and maintains the optimal environment needed to allow the development of transplanted cells. 相似文献