全文获取类型
收费全文 | 1234篇 |
免费 | 60篇 |
国内免费 | 10篇 |
出版年
2023年 | 13篇 |
2022年 | 5篇 |
2021年 | 20篇 |
2020年 | 8篇 |
2019年 | 26篇 |
2018年 | 16篇 |
2017年 | 14篇 |
2016年 | 17篇 |
2015年 | 61篇 |
2014年 | 151篇 |
2013年 | 166篇 |
2012年 | 172篇 |
2011年 | 112篇 |
2010年 | 73篇 |
2009年 | 31篇 |
2008年 | 29篇 |
2007年 | 36篇 |
2006年 | 25篇 |
2005年 | 25篇 |
2004年 | 21篇 |
2003年 | 27篇 |
2002年 | 30篇 |
2001年 | 14篇 |
2000年 | 14篇 |
1999年 | 10篇 |
1998年 | 9篇 |
1997年 | 15篇 |
1996年 | 19篇 |
1995年 | 14篇 |
1994年 | 18篇 |
1993年 | 11篇 |
1992年 | 11篇 |
1991年 | 13篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1988年 | 8篇 |
1987年 | 8篇 |
1986年 | 3篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1971年 | 5篇 |
1970年 | 2篇 |
排序方式: 共有1304条查询结果,搜索用时 15 毫秒
1.
Stefano Carenini Dirk Montag Harold Cremer Melitta Schachner Rudolf Martini 《Cell and tissue research》1996,287(1):3-9
We have previously shown that mice deficient in the gene for the myelin-associated glycoprotein (MAG) develop normal myelin
in the peripheral nerves, but show axon and myelin degeneration at eight months of age, suggesting that MAG is involved in
the maintenance of axon-Schwann cell integrity. The search for molecules that might replace MAG during myelination revealed
an overexpression of the neural cell adhesion molecule (N-CAM) at those aspects where MAG is detectable in wild type mice.
To test whether N-CAM might compensate for MAG during myelination in MAG-deficient mice, double mutants deficient in both
MAG and N-CAM (MAG−/N-CAM−mice) were generated by cross-breeding the single mutants. Whereas alterations of myelin development were not detectable in
either of the single or double mutants, degeneration of myelin and axons occurred approximately 4 weeks earlier in MAG−/N-CAM−than in MAG−mutants. Furthermore, at 8 weeks of age, single fiber preparation and electron microscopy revealed that the number of profiles
indicative of degeneration was substantially increased in MAG−/N-CAM−mutants when compared to MAG−mice. These data suggest that in MAG-deficient mice N-CAM does not compensate for MAG in myelin formation but partially substitutes
for it in the maintenance of axon-myelin integrity.
Received: 20 May 1996 / Accepted: 19 July 1996 相似文献
2.
Monica L. Gavala Lindsay M. Hill Lisa Y. Lenertz Maya R. Karta Paul J. Bertics 《The Journal of biological chemistry》2010,285(44):34288-34298
Activation of the ionotropic P2RX7 nucleotide receptor by extracellular ATP has been implicated in modulating inflammatory disease progression. Continuous exposure of P2RX7 to ligand can result in apoptosis in many cell types, including monocytic cells, whereas transient activation of P2RX7 is linked to inflammatory mediator production and the promotion of cell growth. Given the rapid hydrolysis of ATP in the circulation and interstitial space, transient activation of P2RX7 appears critically important for its action, yet its effects on gene expression are unclear. The present study demonstrates that short-term stimulation of human and mouse monocytic cells as well as mouse osteoblasts with P2RX7 agonists substantially induces the expression of several activating protein-1 (AP-1) members, particularly FosB. The potent activation of FosB after P2RX7 stimulation is especially noteworthy considering that little is known concerning the role of FosB in immunological regulation. Interestingly, the magnitude of FosB activation induced by P2RX7 stimulation appears greater than that observed with other known inducers of FosB expression. In addition, we have identified a previously unrecognized role for FosB in osteoblasts with respect to nucleotide-induced expression of cyclooxygenase-2 (COX-2), which is the rate-limiting enzyme in prostaglandin biosynthesis from arachidonic acid and is critical for osteoblastic differentiation and immune behavior. The present studies are the first to link P2RX7 action to FosB/AP-1 regulation in multiple cell types, including a role in nucleotide-induced COX-2 expression, and support a role for FosB in the control of immune and osteogenic function by P2RX7. 相似文献
3.
宫颈癌患者外周血CD4+CD25+high调节性T细胞的表达及意义 总被引:1,自引:0,他引:1
目的:探讨宫颈癌患者外周血中CD4~ CD25~( high)调节性T(regulator T cells,Tr)的表达及意义。方法:采用流式细胞术检测52例宫颈癌患者,35例健康女性外周血中CD4~ CD25~( high)Tr、细胞毒性T细胞(cytotoxic T lymphocytes,CTL)和NK细胞,采用ELISA检测血清中-干扰素(interferon,IFN-)的表达水平。结果:宫颈癌患者外周血CD4~ CD25~( high)Tr占CD4~ T淋巴细胞的百分比为(7.18±2.32)%,高于健康女性组(P<0.05);宫颈癌患者外周血CD4~ CD25~( high)Tr水平与CTL、NK细胞及IFN-水平呈负相关。结论:宫颈癌患者外周血中具免疫抑制活性的CD4~ CD25~( high)Tr水平较高,参与宫颈癌患者的肿瘤免疫抑制。 相似文献
4.
Bo Lin Dipika Gupta Christopher D. Heinen 《The Journal of biological chemistry》2014,289(35):24314-24324
Human pluripotent stem cells (PSCs) are presumed to have robust DNA repair pathways to ensure genome stability. PSCs likely need to protect against mutations that would otherwise be propagated throughout all tissues of the developing embryo. How these cells respond to genotoxic stress has only recently begun to be investigated. Although PSCs appear to respond to certain forms of damage more efficiently than somatic cells, some DNA damage response pathways such as the replication stress response may be lacking. Not all DNA repair pathways, including the DNA mismatch repair (MMR) pathway, have been well characterized in PSCs to date. MMR maintains genomic stability by repairing DNA polymerase errors. MMR is also involved in the induction of cell cycle arrest and apoptosis in response to certain exogenous DNA-damaging agents. Here, we examined MMR function in PSCs. We have demonstrated that PSCs contain a robust MMR pathway and are highly sensitive to DNA alkylation damage in an MMR-dependent manner. Interestingly, the nature of this alkylation response differs from that previously reported in somatic cell types. In somatic cells, a permanent G2/M cell cycle arrest is induced in the second cell cycle after DNA damage. The PSCs, however, directly undergo apoptosis in the first cell cycle. This response reveals that PSCs rely on apoptotic cell death as an important defense to avoid mutation accumulation. Our results also suggest an alternative molecular mechanism by which the MMR pathway can induce a response to DNA damage that may have implications for tumorigenesis. 相似文献
5.
《Developmental cell》2021,56(17):2516-2535.e8
6.
Extravasation of circulating cells from the bloodstream plays a central role in many physiological and pathophysiological processes, including stem cell homing and tumor metastasis. The three-dimensional flow chamber device (hereafter the 3D device) is a novel in vitro technology that recreates physiological shear stress and allows each step of the cell extravasation cascade to be quantified. The 3D device consists of an upper compartment in which the cells of interest circulate under shear stress, and a lower compartment of static wells that contain the chemoattractants of interest. The two compartments are separated by porous inserts coated with a monolayer of endothelial cells (EC). An optional second insert with microenvironmental cells of interest can be placed immediately beneath the EC layer. A gas exchange unit allows the optimal CO2 tension to be maintained and provides an access point to add or withdraw cells or compounds during the experiment. The test cells circulate in the upper compartment at the desired shear stress (flow rate) controlled by a peristaltic pump. At the end of the experiment, the circulating and migrated cells are collected for further analyses. The 3D device can be used to examine cell rolling on and adhesion to EC under shear stress, transmigration in response to chemokine gradients, resistance to shear stress, cluster formation, and cell survival. In addition, the optional second insert allows the effects of crosstalk between EC and microenvironmental cells to be examined. The translational applications of the 3D device include testing of drug candidates that target cell migration and predicting the in vivo behavior of cells after intravenous injection. Thus, the novel 3D device is a versatile and inexpensive tool to study the molecular mechanisms that mediate cellular extravasation. 相似文献
7.
《Saudi Journal of Biological Sciences》2022,29(2):831-839
The survival reduction after transplantation limited the clinical uses of stem cells so the current study explored preconditioning adipose-derived stem cells (ADMSCs) and all-trans retinoic acid (ATRA) effects on cisplatin that caused acute kidney injury (AKI). One hundred and fifty Sprague–Dawley male rats were distributed into five groups: control group; Cisplatin (CIS) group; CIS and ATRA group; CIS and ADMSC group, and CIS, ATRA, and ADMSCs group. Ten rats were euthanized after 3rd, 7th, and 11th days from CIS injection. Renal function, molecular studies, and histopathological analysis were studied. The preconditioning of ADMSCs with ATRA increased the viability of the cells which was reflected in the amelioration of kidney functions after CIS injection by the significant reduction of serum creatinine, microalbuminuria, as well as NO, and the significant rise of creatinine clearance, as well as SOD compared to the group of cisplatin. ATRA also supported ADMSCs by a significant down-regulation of caspase-3, il-6 and TGFβ1, and a significant up-regulation of HIF1, VEGF and CD31 compared to group of cisplatin which reversed the cisplatin effect. ATRA increased renoprotective properties of ADMSCs against cisplatin- induced AKI by reducing the apoptosis, inflammation, and stimulating angiogenesis. 相似文献
8.
9.
10.
Elevated levels of many metals are toxic to plant roots, but their modes of action are not well understood. We investigated
the toxicities of aluminium (Al), copper (Cu), and lanthanum (La) in solution on the growth and external morphology of 3-d-old
cowpea (Vigna unguiculata L.) roots for periods of up to 48 h. Root elongation rate decreased by 50% at ca. 30 μM Al, 0.3 μM Cu, or 2.0 μM La, accompanied
by a decrease in the distance from the root tip to the proximal lateral root. Kinks developed in some roots 2.0 ± 0.4 mm from
the root apex on exposure to Al or La (but not Cu). Light and scanning electron microscopy showed that soluble Al, Cu, or
La caused similar transverse ruptures to develop > 1 mm from the root apex through the breaking and separation of the rhizodermis
and outer cortex from inner-layers. The metals differed, however, in the range in concentration at which they had this effect;
developing in solutions containing 54 to‑600 μM Al, but only from 0.85 to 1.8 μM Cu or 2.0 to 5.5 μM La. These findings suggest
that Al, Cu, and La bind to the walls of cells, causing increased cell wall rigidity and eventual cell rupturing of the rhizodermis
and outer cortex in the elongating zone. We propose that this is a major toxic effect of Al, and that Cu and La also have
additional toxic effects. 相似文献