全文获取类型
收费全文 | 772篇 |
免费 | 24篇 |
国内免费 | 75篇 |
专业分类
系统科学 | 13篇 |
丛书文集 | 18篇 |
教育与普及 | 16篇 |
现状及发展 | 193篇 |
综合类 | 630篇 |
自然研究 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 10篇 |
2019年 | 7篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 16篇 |
2014年 | 26篇 |
2013年 | 18篇 |
2012年 | 32篇 |
2011年 | 31篇 |
2010年 | 25篇 |
2009年 | 37篇 |
2008年 | 46篇 |
2007年 | 53篇 |
2006年 | 51篇 |
2005年 | 50篇 |
2004年 | 37篇 |
2003年 | 44篇 |
2002年 | 54篇 |
2001年 | 49篇 |
2000年 | 31篇 |
1999年 | 38篇 |
1998年 | 25篇 |
1997年 | 31篇 |
1996年 | 18篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 14篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1980年 | 1篇 |
排序方式: 共有871条查询结果,搜索用时 781 毫秒
1.
2.
Science Letters: A synthetic Toll-like receptor 2 ligand decreases allergic immune responses in a mouse rhinitis model sensitized to mite allergen 下载免费PDF全文
It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported to modulate the balance of Th1/Th2 responses. We evaluated the modulation effect of Pam3CSK4 on allergic immune response in a mouse rhinitis model sensitized to house dust mite allergen (HDM). Mice were sensitized and challenged with Dermatophagoidesfarinae allergen (Der f), and then the allergic mice were treated by Pam3CSK4. Nasal allergic symptoms and eosinophils were scored. Der f-specific cytokine responses were examined in the splenocytes and bronchoalveolar lavage fluid (BALF). Serum level of total IgE was also detected. After establishing a mouse allergic rhinitis model with HDM, we have showed that Pam3CSK4 treatment not only ameliorated the nasal allergic symptoms remarkably but also decreased the eosinophils and total inflammation cells in BALF significantly. Analysis of cytokine profile found that IFN-7 released from either BALF or stimulated splenocytes increased markedly in Pam3CSK4-treated mice, while IL-13 decreased significantly. Moreover, serum level of total IgE was significantly lower in Pam3CSK4-treated mice than in the untreated. Thus, in an allergic rhinitis mouse model developed with HDM, Pam3CSK4 was shown to exhibit an antiallergic effect, indicating its potential application in allergic diseases. 相似文献
3.
《科学通报(英文版)》2008,(19)
The purposes of this research were to study the stable expression of exogenous gene encoding therapeutic protein in attenuated Salmonella typhimurium, observe the metabolism of oral gene vaccine carried by attenuated Salmonella typhimurium in BALB/c mouse, and investigate the feasibility of prevention and treatment of tumors by the recombinant bacteria. Recombinant plasmid pcDNA3.1 VEGFR2(n1-7) was transformed into competent attenuated Salmonella typhimurium SL3261 to develop oral DNA vaccine SL3261-pcDNA3.1 VEGFR2(n1-7). To observe whether the exogenous gene can be expressed in the recombinant bacteria, PCR was performed to amplify the CMV promoter of the eukaryotic expression vector as the proof of stable expression of exogenous protein; transmission elec- tron microscopy (TEM) was applied to observe the morphology of the recombinant bacteria to confirm that the exogenous gene has no impact on the growth of the bacteria, and then BALB/c mice were immunized with the gene vaccine. After inoculation of the gene vaccine, the recombinant bacteria SL3261 could be detected in the tissues such as small intestine, colon, liver and spleen. And then, mice in each group were challenged with tumor cells. The results of animal experiment showed that tumor growth of the mice in experimental group was inhibited and survival time of immunized mice was prolonged compared with control groups. A higher lymphocyte infiltration in tumors from animals treated with DNA vaccine was observed. Immunohistochemical analysis of tumor samples revealed an en- hanced accumulation of CD8 cytotoxic T lymphocytes, as well as an increase in CD4 cells in the tumors of animals treated with the oral gene vaccine compared to tumors from control group mice. Ultrastructure of the tumor tissue showed that tumor cells in the samples of the immunized mice were well-differentiated. Our research confirmed that the exogenous gene can be stably expressed in the attenuated Salmonella typhimurium and has no impact on the growth of the recombinant bacteria; the exogenous gene can de delivered to the host by attenuated Salmonella typhimurium to produce anti-tumor effect with no obvious cytotoxity to the host. In this study, it is established that attenuated Salmonella typhimurium could be used as a vector for oral gene vaccine, and our study provided a theoretical basis for the body distribution and the metabolism of the recombinant bacteria. This strategy may provide a simple, safe and effective way for the prevention and treatment of tumors. 相似文献
4.
Growth hormone signal transduction 总被引:1,自引:0,他引:1
Growth hormone (GH) promotes animal growth by stimulating bone and cartilage cell proliferation, and influences carbohydrate and lipid metabolism. Some of these effects are brought about indirectly via somatomedin induction in hepatocytes, others by acting directly on the target cells. In either case, GH first binds to specific receptors on cells to trigger a sequence of biochemical events culminating in a biological response. Recently much has been learnt about the molecular structure of GH receptor, its binding to ligand, and the ensuing signal transduction events. 相似文献
5.
介绍了高速公路不停车收费系统方案,阐述了该系统的结构、组成、模块功能以及它们的相互关系,并探讨了该系统设计的基本原则。 相似文献
6.
M. T. Santini R. Masella A. Cantafora S. W. Peterson 《Cellular and molecular life sciences : CMLS》1992,48(1):36-39
We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T for a 3-h period at 37°C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation. 相似文献
7.
J. -L. Carpentier P. Gorden A. Robert L. Orci 《Cellular and molecular life sciences : CMLS》1986,42(7):734-744
Conclusion The insulin receptor is an integral protein of the plasma membrane of the cell. It is composed of two subunits: an subunit, which binds the hormone, and a subunit which is a tyrosine specific protein kinase capable of undergoing autophosphorylation. These independent subunits are synthesized by way of a higher molecular weight single chain precursor and thus are the product of a single gene29, 49, 85 localized to chromosome 1929, 91. Assuming that the insulin receptor is synthesized in the same fashion as other integral membrane glycoproteins, then the nucleus, the rough endoplasmic reticulum, and the Golgi apparatus are involved in its biosynthesis. Further, there must be some form of transport of the mature receptor subunits to the plasma membrane where they are inserted.By contrast, the endocytotic route involves coated pits, coated vesicles, large clear vesicles or endosomes, multivesicular bodies and other lysosomal forms. In addition, it is possible that some other as yet unidentified organelle is involved in recycling (fig. 8). At the present time, with respect to the insulin receptor, the biosynthetic pathway and the endocytotic pathway appear to be separate. Further, it does not appear that either pathway, i. e. synthesis or endocytosis, exerts a regulatory function over the other. 相似文献
8.
V. Pli<ska 《Cellular and molecular life sciences : CMLS》1991,47(3):216-221
Summary Binding studies in various biological systems frequently indicate the presence of several binding sites for a biologically active ligand. They differ in their affinity for the ligand in question, binding capacity, and Hill coefficient, which suggests differences in the mechanisms of the binding site-ligand interactions. Identification of the true receptors (sites initiating a cellular response) appears to be difficult. Three clusters of binding sites for oxytocin were found on rat myometrial cells. The oxytocin receptor seems to be linked to the medium-affinity site; the cooperation between the high-and medium-affinity sites in eliciting the uterotonic response seems likely, but lacks experimental proof. Dose-response analysis in partially irreversibly inhibited uterus preparations, the method of equipotent doses (Furchgott-Bursztyn method), and structure-activity analysis of oxytocin-like peptides acting as competitive inhibitors of oxytocin, turned out to be suitable for pharmacological analysis of this receptor system. 相似文献
9.
X. Wang C. A. Lessman D. B. Taylor T. K. Gartner 《Cellular and molecular life sciences : CMLS》1995,51(11):1097-1102
Gastrulation is characterized by dramatic cell migration which is thought to require the interaction of cell adhesion molecules with extracellular molecules. We have tested two novel peptides, a fibronectin peptide and a fibronectin receptor peptide, for their effects on gastrulation of the leopard frogRana pipiens. The fibronectin peptide DRVPHSRNSIT corresponds to residues 1373–1383 of the cell-binding domain of fibronectin; the receptor peptide DLYYLMDL corresponds to residues 124–131 of 1 subunit of a variety of integrins including 51. Either of these peptides significantly inhibited gastrulation after being microinjected into mid-blastulae. These results indicate that these sequences may correspond to the ligand/receptor interaction sites of fibronectin and its receptor(s). 相似文献
10.
Colony-stimulating factor-1 (CSF-1), which is necessary for cell proliferation and differentiation, regulates both immediate
and delayed early responses throughout G1 phase. The binding of CSF-1 to its receptor (CSF-1R) triggers phosphorylation of
the receptor and its intrinsic tyrosine kinase. The activated receptor binds directly to cytoplasmic effector proteins, which
induce multiple-signal transduction pathways. CSF-1 can induce the c-myc gene expression via Ras and Ets-related proteins.
The expression of c-fos/jun family genes is also targeted following the activation of Ras. CSF-1R activates STAT1 and STAT3
to participate in signaling, but JAKs do not appear to contribute to signaling by CSF-1R. CSF-1R activates PI3-kinase, and
PI3-ki can interact with downstream proteins by the MAPKK-related pathway independent of Ras/Raf. PC-PLC can enforce signaling
in response to CSF-1. Furthermore, the turnover and dephosphorylation by the phosphatase SHPTP1 of CSF-1R are the major mechanism
in the negative regulation of signaling by CSF-1R 相似文献