全文获取类型
收费全文 | 998篇 |
免费 | 76篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 21篇 |
2020年 | 9篇 |
2019年 | 18篇 |
2018年 | 15篇 |
2017年 | 31篇 |
2016年 | 31篇 |
2015年 | 51篇 |
2014年 | 55篇 |
2013年 | 68篇 |
2012年 | 86篇 |
2011年 | 83篇 |
2010年 | 54篇 |
2009年 | 44篇 |
2008年 | 61篇 |
2007年 | 57篇 |
2006年 | 50篇 |
2005年 | 49篇 |
2004年 | 62篇 |
2003年 | 53篇 |
2002年 | 44篇 |
2001年 | 20篇 |
2000年 | 3篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 11篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1974年 | 1篇 |
1968年 | 1篇 |
1940年 | 1篇 |
1936年 | 1篇 |
1931年 | 1篇 |
1912年 | 2篇 |
1908年 | 1篇 |
排序方式: 共有1074条查询结果,搜索用时 15 毫秒
121.
Myeloid leukocytes are the first line of host defence. When they sense perturbations in tissue homeostasis such as infection, inflammation and ischemia, they respond by trafficking. Whilst neutrophils and macrophages migrate to sites of infection, dendritic cells (DC) migrate from tissue-resident sites back into lymph nodes where they activate T and B lymphocytes. The directed migration of these leukocytes through peripheral tissues is thus crucial for their function. This article considers recent advances in our understanding of the adhesive and motile behaviour of macrophages and DC, with particular emphasis on the podosomes that appear to be required for normal migration through extracellular matrices. 相似文献
122.
VCAM-1 is one of the main ligands of VLA-4, an integrin that is highly expressed on the surface of mature B cells. Here we find that coexpression of VCAM-1 on an antigen-bearing membrane facilitates B-cell activation. Firstly, this is achieved by mediating B-cell tethering, which in turn increases the likelihood of a B cell to be activated. Secondly, VLA-4 synergizes with the B-cell receptor (BCR), providing B cells with tight adhesion and enhanced signalling. This dual role of VCAM-1 in promoting B-cell activation is predominantly effective when the affinity of the BCR for the antigen is low. In addition, we show that the VCAM-1 ectodomain alone is sufficient to carry out this function. However, it requires the transmembrane domain to segregate properly into a docking structure characteristic of the B-cell immunological synapse (IS). These results show that the VLA-4/VCAM-1 interaction during membrane antigen recognition enhances B-cell activation and this function appears to be independent of its final peripheral localization at the IS. 相似文献
123.
A new species of zephyrinid nudibranch of the genus Janolus Bergh 1884 is described from the Pacific Coast of North America and Costa Rica. J. anulatus sp. nov. differs from other species of Janolus by its external and internal morphology. J. anulatus has a brown or white body with pink, white, and brown spots, smooth papillae epithelium at the base and papillated in the distal part, unbranched digestive gland ducts, smooth jaws, and smooth rachidian and lateral teeth. The species is compared with other species from the Panamic Province and the Western Atlantic. A new extension range of J. barbarensis is documented. 相似文献
124.
125.
Ortega A Romero M Izquierdo A Troyano N Arce Y Ardura JA Arenas MI Bover J Esbrit P Bosch RJ 《Journal of cellular physiology》2012,227(5):1980-1987
Hypertrophy of human mesangial cells (HMC) is among the earliest characteristics in patients with diabetic nephropathy (DN). Recently, we observed the upregulation of parathyroid hormone (PTH)-related protein (PTHrP) in experimental DN, associated with renal hypertrophy. Herein, we first examined whether PTHrP was overexpressed in human DN, and next assessed the putative role of this protein on high glucose (HG)-induced HMC hypertrophy. As previously found in mice, kidneys from diabetic patients showed an increased tubular and glomerular immunostaining for PTHrP. In HMC, HG medium increased PTHrP protein expression associated with the development of hypertrophy as assessed by cell protein content. This effect was also induced by PTHrP(1-36). HG and PTHrP(1-36)-induced hypertrophy were associated with an increase in cyclin D1 and p27Kip1 protein expression, a decreased cyclin E expression, and the prevention of cyclin E/cdk2 complex activation. Both PTHrP neutralizing antiserum (α-PTHrP) and the PTH/PTHrP receptor antagonist (JB4250) were able to abolish HG induction of hypertrophy, the aforementioned changes in cell cycle proteins, and also TGF-β1 up-regulation. Moreover, the capability of both HG and PTHrP(1-36) to induce HMC hypertrophy was abolished by α-TGFβ1. These data show for the first time that PTHrP is upregulated in the kidney of patients with DN. Our findings also demonstrate that PTHrP acts as an important mediator of HG-induced HMC hypertrophy by modulating cell cycle regulatory proteins and TGF-β1. 相似文献
126.
García-Posadas L Contreras-Ruiz L López-García A Villarón Álvarez S Maldonado MJ Diebold Y 《Histochemistry and cell biology》2012,137(2):165-176
The purpose of this study was to demonstrate the presence of the receptor for hyaluronan-mediated motility (RHAMM) in human
conjunctival epithelium and in two widely used cell lines from human corneal (HCE) and conjunctival (IOBA-NHC) epithelia.
We compared the distribution of RHAMM proteins and mRNAs in human ocular surface tissues (corneal, limbal and conjunctival),
HCE and IOBA-NHC cell lines, and corneal and conjunctival epithelia primary samples from healthy donors with the previously
identified hyaluronan receptor CD44. We also aimed to determine if soluble CD44 (sCD44) was present in human tears, as it
could have a role in the interaction of the tear fluid with hyaluronan. Protein expression was evaluated by Western blots
and immunofluorescence microscopy. mRNA expression was evaluated by RT-PCR and Q-PCR. sCD44 was analyzed by ELISA in culture
supernatants and in human tears. We describe the expression of RHAMM in human healthy conjunctiva and in HCE and IOBA-NHC
cells at both protein and mRNA levels, and the presence of sCD44 in human tears. Furthermore, we detected CD44 and sCD44 expression
variations in in vitro inflammatory conditions. This study also focused on the necessary caution with which the conclusions
extracted from cell lines should be made, and in the great value of using primary samples as often as possible. 相似文献
127.
López-Chicón P Paz-Cristobal MP Rezusta A Aspiroz C Royo-Ca?as M Andres-Ciriano E Gilaberte Y Agut M Nonell S 《Photochemical & photobiological sciences》2012,11(6):1099-1107
The photoprocesses involved in hypericin photoinactivation of three different Candida species (C. albicans, C. parapsilosis and C. krusei) have been examined. Production of singlet oxygen from the triplet state and of superoxide from both the triplet state and the semiquinone radical anion are demonstrated. Hydrogen peroxide is formed downstream of these early events. The outcome of the photodynamic treatments is dictated by the intracellular distribution of hypericin, which is different in the three species and affects the ability of hypericin to produce the different reactive oxygen species and trigger cell-death pathways. The results are in line with the previously-observed different susceptibilities of the three Candida species to hypericin photodynamic treatments. 相似文献
128.
129.
HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep:activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest:activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels. 相似文献
130.
Estefania Calvo-álvarez Nestor Adrian Guerrero Raquel álvarez-Velilla Christopher Fernández Prada Jose María Requena Carmen Punzón Miguel ángel Llamas Francisco J. Arévalo Luis Rivas Manuel Fresno Yolanda Pérez-Pertejo Rafael Bala?a-Fouce Rosa M. Reguera 《PLoS neglected tropical diseases》2012,6(11)