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841.
The discovery of dendritic cells (DCs) as professional antigen presenting cells has opened up new possibilities for their use in the development of tumor vaccines. We investigated the effect of the CD8α+ DCs loaded with heat-treated tumor lysate (HTL) as a vaccine in tumor immunotherapy. The HTL loaded CD8α+ DCs, TL loaded CD8α+ DCs and unloaded CD8α+ DCs were subcutaneously injected in the fibrosarcoma-bearing mice. The splenocyte proliferation and the shifting of Th1/Th2 response were measured. The results indicated a significant increase in the lymphocytes proliferation and the IFN-γ production in the test group of mouse splenocytes. According to the results, HTL loaded CD8α+ DCs vaccine significantly decreased tumor growth and longer survival than the other immunized animals. These findings show that anti-tumor immune response against the fibrosarcoma can be induced by HTL loaded CD8α+ DCs and may provide a useful therapeutic model for development of approaches to tumor treatments. 相似文献
842.
Interferon γ (IFNγ) plays a central role in the immune response against infection and tumur immune surveillance. Its functions include not only activation of the host immune system to control microbial infections but also repression of autoimmune responses by turning on T-regulatory cells and increasing T effector cell apoptosis. Defects in IFNγ and IFNγ receptor genes have been associated with autoimmune diseases such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis. However, treatment of autoimmune diseases by supplementing with IFNγ has been satisfactory due to its broad biological effects. Instead, its target T-regulatory cells may be used for the clinical treatment of autoimmune diseases. Future study could also focus on promotion of the beneficial effects of IFNγ and blocking those unwanted IFNγ-induced activities. 相似文献
843.
Trafficking and function of the tetraspanin CD63 总被引:2,自引:0,他引:2
Tetraspanins comprise a large superfamily of cell surface-associated membrane proteins characterized by four transmembrane domains. They participate in a variety of cellular processes, like cell activation, adhesion, differentiation and tumour invasion. At the cell surface, tetraspanins form networks with a wide diversity of proteins called tetraspanin-enriched microdomains (TEMs). CD63 was the first characterized tetraspanin. In addition to its presence in TEMs, CD63 is also abundantly present in late endosomes and lysosomes. CD63 at the cell surface is endocytosed via a clathrin-dependent pathway, although recent studies suggest the involvement of other pathways as well and we here present evidence for a role of caveolae in CD63 endocytosis. In late endosomes, CD63 is enriched on the intraluminal vesicles, which by specialized cells are secreted as exosomes through fusion of endosomes with the plasma membrane. The complex localization pattern of CD63 suggests that its intracellular trafficking and distribution must be tightly regulated. In this review we discuss the latest insights in CD63 trafficking and its emerging function as a transport regulator of its interaction partners. Finally, the involvement of CD63 in cancer will be discussed. 相似文献
844.
845.
Ing-Marie Viklund Pontus Aspenström Vannary Meas-Yedid Jolanta Kopec Daniel Ågren Gunter Schneider Mauro D'Amato Jean-Christophe Olivo-Marin Guy Tran Van Nhieu Sven Pettersson 《Experimental cell research》2009,315(6):1040-220
We have previously identified a new gene with sequence homology to the WASP-family of actin regulators denoted WAFL (WASP and FKBP-like). Here we report a possible biological function for WAFL, by demonstrating an association to early endosomes via its central coiled-coil domain. Further we show by functional and structural studies that WAFL is associated with both microtubules and the actin filament system, the two means of transport of early endosomes. In addition, WAFL interacts with WASP-interacting protein (WIP) and actin, thus linking WAFL to actin dynamics. The use of RNAi depletion of WAFL shows that WAFL-deficient cells display delayed transport of endosomal cargo. Our findings are compatible with a model whereby WAFL is involved in the transport of early endosomes at the level of transition between microfilament-based and microtubule-based movement. 相似文献
846.
Bolscher JG Adão R Nazmi K van den Keybus PA van 't Hof W Nieuw Amerongen AV Bastos M Veerman EC 《Biochimie》2009,91(1):123-132
The innate immunity factor lactoferrin harbours two antimicrobial moieties, lactoferricin and lactoferrampin, situated in close proximity in the N1 domain of the molecule. Most likely they cooperate in many of the beneficial activities of lactoferrin. To investigate whether chimerization of both peptides forms a functional unit we designed a chimerical structure containing lactoferricin amino acids 17-30 and lactoferrampin amino acids 265-284. The bactericidal activity of this LFchimera was found to be drastically stronger than that of the constituent peptides, as was demonstrated by the need for lower dose, shorter incubation time and less ionic strength dependency. Likewise, strongly enhanced interaction with negatively charged model membranes was found for the LFchimera relative to the constituent peptides. Thus, chimerization of the two antimicrobial peptides resembling their structural orientation in the native molecule strikingly improves their biological activity. 相似文献
847.
Genetic material obtained from various individuals may contain certain polymorphisms which may conflict with the predetermined
DNA sequence and consequently, may modulate the function of gene products. In this study, coding sequence of rat CD40 ligand
(CD40L, CD154) was obtained from activated splenocytes, amplified, and cloned into a eukaryotic expression vector by using
directional cloning method. Sequence of the recombinant rat CD40L DNA, pCD40L-IRES2-EGFP (pCD40L), was compared with the previously
reported rat CD40L cDNA sequences and a 99% identity was found. Differing nucleotides were on the positions; 122-T/C, 341-G/A,
476-G/A, 762-T/A. Further alignment analysis showed that pCD40L was collectively carrying the nucleotides each previously
reported by different groups. The sequence was submitted to NCBI GenBank and nucleotide database accession number EF066490
was obtained. Following transfection of the construct into NIH/3T3 cell line, novel CD40L clone was functionally expressed
de novo, increasing the expression of CD80 and CD86 costimulatory molecules and augmenting the proliferation rate of effector
splenocytes in immune reactions ex vivo. Based on these data, here we report a novel recombinant clone of the rat CD40L gene
which may represent a potential polymorphic variant. 相似文献
848.
Spermatogonial stem cells (SSCs) are a documented source for adult multipotent stem cells. Thus, the isolation of SSCs is
of great interest. However, the isolation of spermatogonia from mammalian testes is difficult because of their low total numbers
and the lack of well-characterized cell surface markers. Glial-cell-derived neurotrophic factor family receptor alpha-1 (GFRα1)
is expressed on undifferentiated mouse spermatogonia (including SSCs) and plays a crucial role, in rodents, for the maintenance
of SSCs mediated by the Sertoli cell product GDNF. The present study has aimed to optimize the sorting efficiency and total
cell yield of magnetic activated cell sorting (MACS) with anti-GFRα1 antibodies. Because of the technical limitations intrinsic
to the magnetic columns, various sorting setups and strategies were compared. Use of Mini-MACS (MS) columns for single cell
suspensions from 7-day-old rat testes resulted in a three-fold enrichment of GFRα1-positive cells in sorted fractions versus
presorted fractions. However, with this method, only 1.77% of cells loaded onto the column were recovered in the sorted fraction.
A sequential two-step sorting approach did not improve this poor yield. We therefore evaluated cell separation by using larger
volume Midi-MACS (LS) columns. Enrichment of GFRα1-positive cells in sorted fractions was four-fold, and 14.5% of cells loaded
onto the column were directed to the sorted fraction. With this method, approximately half of all GFRα1-positive cells present
in the sample were found in the sorted fraction. We conclude that GFRα1 serves as a suitable surface marker for the enrichment
of rat spermatogonia, and that the large-volume Midi-MACS separation system is superior to the routinely used small-volume
Mini-MACS separation system.
This work was financially supported by startup funds from the University Münster, NIH grant U54 HD 008610, Center grant, project
1 (to S.S.), a doctoral scholarship from the Ernst Schering Research Foundation (to K.G.), and a Young Investigator Grant
from the Lance Armstrong Foundation (to J.E.). 相似文献
849.
Julia Knöckel Rositsa Jordanova Ingrid B. Müller Carsten Wrenger Matthew R. Groves 《Biochimica et Biophysica Acta (BBA)/General Subjects》2009
Background
Vitamin B6 synthesis requires a functional Pdx1 assembly that is dodecameric in vivo. We have previously shown that mutation of a catalytic lysine in the plasmodial Pdx1 protein results in a protein that is both inactive and hexameric in vitro.Methods
Static and dynamic light scattering, circular dichroism, co-purification and enzyme assays are used to investigate the role of a glycine conserved in all Pdx1 family members.Results
Static light scattering indicates that a glycine to alanine mutant is present as a hexamer in vitro. Subsequent circular dichroism experiments demonstrate that a significant change in secondary structure content is induced by this mutation. However, this mutant is still competent to bind and support Pdx2 activity.Conclusions
As the mutated glycine occupies an unrestricted region of the Ramachandran plot the additional stereo-chemical restrictions imposed on alanine residues strongly support our hypothesis that significant structural rearrangement of Pdx1 is required during the transition from hexamer to dodecamer.General significance
The presented results demonstrate that reduction in the mobility of this region in Pdx1 proteins is required for formation of the in vivo dodecamer, negatively affecting the activity of Pdx1, opening the possibility of allosteric Pdx1 inhibitors. 相似文献850.
Allal Ouhtit Rajiv L. Gaur Zakaria Y. Abd Elmageed Augusta Fernando Rajesh Thouta Alison K. Trappey Mohamed E. Abdraboh Hassan I. El-Sayyad Prakash Rao Madhwa G.H. Raj 《生物化学与生物物理学报:癌评论》2009
CD146, also known as melanoma cell adhesion molecule or MCAM, is a key cell adhesion protein in vascular endothelial cell activity and angiogenesis. CD146 promotes tumor progression of many cancers including melanoma and prostate. Strikingly, its expression is frequently lost in breast carcinoma cells, and it may act as a suppressor of breast cancer progression. While upstream mechanisms regulating CD146 are well documented, our understanding of the downstream molecular events underlying its mode of action remains to be elucidated. This review aims to focus on the progress in understanding the signaling mechanisms and the functional relevance of CD146, a multifaceted molecule, in cancer with particular emphasis on its role in inhibiting breast cancer progression. 相似文献