全文获取类型
收费全文 | 7388篇 |
免费 | 223篇 |
国内免费 | 261篇 |
出版年
2023年 | 48篇 |
2022年 | 91篇 |
2021年 | 116篇 |
2020年 | 97篇 |
2019年 | 170篇 |
2018年 | 216篇 |
2017年 | 99篇 |
2016年 | 111篇 |
2015年 | 158篇 |
2014年 | 404篇 |
2013年 | 495篇 |
2012年 | 272篇 |
2011年 | 427篇 |
2010年 | 258篇 |
2009年 | 385篇 |
2008年 | 424篇 |
2007年 | 398篇 |
2006年 | 402篇 |
2005年 | 403篇 |
2004年 | 340篇 |
2003年 | 304篇 |
2002年 | 254篇 |
2001年 | 157篇 |
2000年 | 169篇 |
1999年 | 177篇 |
1998年 | 169篇 |
1997年 | 155篇 |
1996年 | 125篇 |
1995年 | 136篇 |
1994年 | 99篇 |
1993年 | 75篇 |
1992年 | 77篇 |
1991年 | 64篇 |
1990年 | 57篇 |
1989年 | 50篇 |
1988年 | 56篇 |
1987年 | 47篇 |
1986年 | 35篇 |
1985年 | 53篇 |
1984年 | 53篇 |
1983年 | 38篇 |
1982年 | 31篇 |
1981年 | 30篇 |
1980年 | 27篇 |
1979年 | 25篇 |
1978年 | 16篇 |
1977年 | 17篇 |
1976年 | 21篇 |
1975年 | 11篇 |
1974年 | 13篇 |
排序方式: 共有7872条查询结果,搜索用时 15 毫秒
991.
992.
Cantarella G Di Benedetto G Pezzino S Risuglia N Bernardini R 《Journal of neurochemistry》2008,105(5):1915-1923
Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is involved in amyloid beta dependent neurotoxicity via the extrinsic pathway. Recently, several genes modulating TRAIL cytotoxicity have been characterized, providing evidence for a role of wingless-type mouse mammary tumor virus integration site family (Wnt), Jun-N-terminal kinase and other pathways in increased cell susceptibility to the cytokine. We investigated whether neurotoxic effects of TRAIL could be due to modulation of the Wnt signaling pathway. Western blot analysis of Wnt in SH-SY5Y human neuroblastoma cells showed significantly decreased Wnt expression in cultures treated with TRAIL. Correspondingly, both phosphorylation of glycogen synthase kinase 3 beta and degradation of cytoplasmic β-catenin were increased, as well as phosphorylation of the τ protein, bringing about the picture of neuronal damage. As a counterproof of the interaction of TRAIL with the Wnt pathway, the addition of the specific glycogen synthase kinase 3 beta inhibitor SB216763 resulted in rescue of a significant percent of cells from TRAIL-induced apoptosis. The rescue was total when the caspase 8 inhibitor z-IETD-FMK was added in combination with SB216763. Results show that, probably, in addition to triggering caspase signaling, TRAIL also interferes with the Wnt pathway, additionally concurring to neuronal damage. These data suggest that the Wnt pathway substantially contributes to the TRAIL-related neurotoxicity and indicate the TRAIL system as a candidate target for pharmacological treatment of Alzheimer's disease and related disorders. 相似文献
993.
994.
Perbandt M Höppner J Burmeister C Lüersen K Betzel C Liebau E 《Journal of molecular biology》2008,377(2):501-511
Onchocerciasis or river blindness, caused by the filarial worm Onchocerca volvulus, is the world’s second leading infectious cause of blindness. In order to chronically infect the host, O. volvulus has evolved molecular strategies that influence and direct immune responses away from the modes most damaging to it. The O. volvulus GST1 (OvGST1) is a unique glutathione S-transferase (GST) in that it is a glycoprotein and possesses a signal peptide that is cleaved off in the process of maturation. The mature protein starts with a 25-amino-acid extension not present in other GSTs. In all life stages of the filarial worm, it is located directly at the parasite-host interface. Here, the OvGST1 functions as a highly specific glutathione-dependent prostaglandin D synthase (PGDS). The enzyme therefore has the potential to participate in the modulation of immune responses by contributing to the production of parasite-derived prostanoids and restraining the host’s effector responses, making it a tempting target for chemotherapy and vaccine development. Here, we report the crystal structure of the OvGST1 bound to its cofactor glutathione at 2.0 Å resolution. The structure reveals an overall structural homology to the haematopoietic PGDS from vertebrates but, surprisingly, also a large conformational change in the prostaglandin binding pocket. The observed differences reveal a different vicinity of the prostaglandin H2 binding pocket that demands another prostaglandin H2 binding mode to that proposed for the vertebrate PGDS. Finally, a putative substrate binding mode for prostaglandin H2 is postulated based on the observed structural insights. 相似文献
995.
Xu P Yang Y Zhang Z Chen W Zhang C Zhang L Zou S Ma Z 《Journal of experimental botany》2008,59(6):1375-1381
Alterations of mitochondrial-encoded subunits of the FoF1-ATPsynthase are frequently associated with cytoplasmic male sterility(CMS) in plants; however, little is known about the relationshipof the nuclear encoded subunits of this enzyme with CMS. Inthe present study, the full cDNA of the gene TaFAd that encodesthe putative FAd subunit of the FoF1-ATP synthase was isolatedfrom the wheat (Triticum aestivum) fertility restorer 2114for timopheevii cytoplasm-based CMS. The deduced 238 amino acidpolypeptide is highly similar to its counterparts in dicotsand other monocots but has low homology to its mammalian equivalents.TaFAd is a single copy gene in wheat and maps to the short armof the group 6 chromosomes. Transient expression of the TaFAd–GFPfusion in onion epidermal cells demonstrated TaFAd's mitochondriallocation. TaFAd was expressed abundantly in stem, leaf, anther,and ovary tissues of 2114. Nevertheless, its expression wasrepressed in anthers of CMS plants with timopheevii cytoplasm.Genic male sterility did not affect its expression in anthers.The expression of the nuclear gene encoding the 20 kDa subunitof Fo was down-regulated in a manner similar to TaFAd in theT-CMS anthers while that of genes encoding the 6 kDa subunitof Fo and the subunit of F1 was unaffected. These observationsimplied that TaFAd is under mitochondrial retrograde regulationin the anthers of CMS plants with timopheevii cytoplasm. Key words: CMS, FAd subunit, FoF1-ATP synthase, retrograde regulation, wheat
Received 8 October 2007; Revised 9 January 2008 Accepted 28 January 2008 相似文献
996.
997.
Huang X Li Q Zhang Y Lü Q Guo L Huang L He Z 《Cellular and molecular neurobiology》2008,28(4):559-568
1. The neuroprotective effect of cactus polysaccharide (CP) on oxygen and glucose deprivation (OGD) and reoxygenation (REO)-induced
damage in the cortical and hippocampal slices of rat brain was investigated. 2. Cell viability was evaluated by using the
2, 3, 5-triphenyl tetrazolium chloride (TTC) method. The fluorescence of propidium iodide (PI) staining was used for quantification
of cellular survival, and lactate dehydrogenase (LDH) activity in incubation medium was assessed by LDH assay to evaluate
the degree of injury. 3. The OGD ischemic condition significantly decreased cellular viability and increased LDH release in
the incubation medium. CP (0.2 mg/l∼2 mg/l) protected brain slices from OGD injury in a dosage dependent manner as demonstrated
by increased A 490 value of TTC, decreased PI intensity and LDH release. At the above concentration, CP also prevented the increase of nitric
oxide (NO) content and inducible nitric oxide synthase (iNOS) activity induced by OGD. 4. CP can protect the brain slices
(cortical and hippocampus) against injury induced by OGD. Its neuroprotective effect may be partly mediated by the NO/iNOS
system induced by OGD insult.
Xianju Huang and Qin Li have contributed equally to this article. 相似文献
998.
铁过载促进小鼠肝组织发生蛋白质酪氨酸硝化 总被引:3,自引:0,他引:3
蛋白质酪氨酸硝化是一种蛋白质翻译后的修饰,其存在会影响酶的催化活性,细胞信号转导和细胞骨架结构.在铁过载情况下,存在引起蛋白质酪氨酸硝化的有利环境,但目前尚无实验证实.本文运用腹腔注射右旋糖苷铁造成小鼠铁过载模型,通过免疫印迹法发现,在铁过载情况下,肝中诱导型一氧化氮合酶表达显著高于正常对照小鼠;铁过载小鼠肝中总体蛋白质硝化程度高于正常小鼠;铁过载引起的蛋白质酪氨酸硝化有一定的选择性,在铁过载小鼠肝中发现一些新的被硝化蛋白质条带(约 57 kD、 35 kD).上述结果证实,铁过载会促进肝蛋白质酪氨酸硝化. 相似文献
999.
Kulbatski I Mothe AJ Parr AM Kim H Kang CE Bozkurt G Tator CH 《Progress in histochemistry and cytochemistry》2008,43(3):123-176
Traumatic injury to the brain or spinal cord and multiple sclerosis (MS) share a common pathophysiology with regard to axonal demyelination. Despite advances in central nervous system (CNS) repair in experimental animal models, adequate functional recovery has yet to be achieved in patients in response to any of the current strategies. Functional recovery is dependent, in large part, upon remyelination of spared or regenerating axons. The mammalian CNS maintains an endogenous reservoir of glial precursor cells (GPCs), capable of generating new oligodendrocytes and astrocytes. These GPCs are upregulated following traumatic or demyelinating lesions, followed by their differentiation into oligodendrocytes. However, this innate response does not adequately promote remyelination. As a result, researchers have been focusing their efforts on harvesting, culturing, characterizing, and transplanting GPCs into injured regions of the adult mammalian CNS in a variety of animal models of CNS trauma or demyelinating disease. The technical and logistic considerations for transplanting GPCs are extensive and crucial for optimizing and maintaining cell survival before and after transplantation, promoting myelination, and tracking the fate of transplanted cells. This is especially true in trials of GPC transplantation in combination with other strategies such as neutralization of inhibitors to axonal regeneration or remyelination. Overall, such studies improve our understanding and approach to developing clinically relevant therapies for axonal remyelination following traumatic brain injury (TBI) or spinal cord injury (SCI) and demyelinating diseases such as MS. 相似文献
1000.
ATP synthase converts the electrochemical potential at the inner mitochondrial membrane into chemical energy, producing the ATP that powers the cell. Using electron cryo-tomography we show that the ATP synthase of mammalian mitochondria is arranged in long approximately 1-microm rows of dimeric supercomplexes, located at the apex of cristae membranes. The dimer ribbons enforce a strong local curvature on the membrane with a 17-nm outer radius. Calculations of the electrostatic field strength indicate a significant increase in charge density, and thus in the local pH gradient of approximately 0.5 units in regions of high membrane curvature. We conclude that the mitochondrial cristae act as proton traps, and that the proton sink of the ATP synthase at the apex of the compartment favours effective ATP synthesis under proton-limited conditions. We propose that the mitochondrial ATP synthase organises itself into dimer ribbons to optimise its own performance. 相似文献