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171.
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
172.
Alamtaj Samsami Dehaghani Khatere Shahriary Mohammad Amin Kashef Sirous Naeimi Mohammad Javad Fattahi Zahra Mojtahedi Abbas Ghaderi 《Molecular biology reports》2009,36(8):2393-2397
IL-18, initially defined as a potent inducer of IFN- γ production, is a systemic, multifunctional cytokine with both pro-cancerous
and anti-cancer activities. The contribution of the IL-18 promoter polymorphisms at positions −607 (C/A) and −137 (G/C) to
cancer development has been reported. We sought to examine IL-18 serum level and its polymorphisms in Iranian women with ovarian
cancer. Single nucleotide polymorphisms (SNPs) at positions −607 (C/A) and −137 (G/C) were analyzed by allele-specific polymerase
chain reaction in 85 women with ovarian cancer and 158 healthy controls. IL-18 serum level was determined using ELISA method.
No significant association was found between the allele, genotype, and haplotype distributions of the SNPs and ovarian cancer.
Mean IL-18 serum level was significantly higher in patients than in controls (P = 0.008). Comparing IL-18 serum levels with genotypes at positions −607 and −137 revealed no significant difference. No association
was also found between IL-18 levels and the disease stage. In conclusion, our results indicate that IL-18 promoter polymorphisms
at positions −607 (C/A) and −137 (G/C) appear not to confer susceptibility to ovarian cancer in Iranian population; however,
IL-18 serum level increases in ovarian cancer patients. 相似文献
173.
Sameni S Ghayumi MA Mortazavi G Faghih Z Kashef MA Ghaderi A 《Molecular biology reports》2009,36(5):1001-1005
Lung cancer is one of the leading causes of death from cancer. Both immune cells and tumor cells play a key role in lung cancer
immunity by secretion of cytokines and developing type-2 cell-mediated immune response. IL-13 is an immunoregulatory cytokine
affecting tumor immunosurveillance by deviation of immune response from Th1 to Th2. In the present study we sought to determine
the association of single nucleotide polymorphisms (SNPs) of IL-13 gene at positions +2044 (G/A) and −1055 (C/T) and lung cancer. One hundred forty one patients and 113 controls were recruited;
control group was subdivided into smoker and nonsmoker individuals for serum detection. Genotyping was carried out by PCR-RFLP
assay and IL-13 detection by ELISA method. No statistically significant difference was found in the frequency of genotypes,
alleles, and haplotypes at positions +2044 (G/A) and −1055 (C/T) of IL-13 gene between lung cancer patients and controls. Serum level of IL-13 was not detectable in both groups. The results of this
study reveal that although +2044 (G/A) and −1055 (C/T) SNPs in IL-13 are implicated in some pulmonary processes, they do not confer susceptibility to lung cancer in Iranian population. 相似文献
174.
Melissa Paulite Zahra Fakhraai Boris B. Akhremitchev Kerstin Mueller Gilbert C. Walker 《Journal of visualized experiments : JoVE》2009,(33)
This paper aims to instruct the reader in the assembly and operation of an infrared near-field microscope for imaging beyond the diffraction limit. The apertureless near-field microscope is a light scattering-type instrument that provides infrared spectra at circa 20 nm resolution. A complete list of components and a step-by-step protocol for use is provided. Common errors in assembly and instrument tuning are discussed. A representative data set that shows the secondary structure of an amyloid fibril is presented. 相似文献
175.
Mitoxantrone is a potent antitumor drug, widely used in the treatment of various cancers. In the present study, we have investigated
and compared the affinity of anticancer drug, mitoxantrone, to EDTA-soluble chromatin (SE-chromatin), DNA and histones employing
UV/Vis, fluorescence, CD spectroscopy, gel electrophoresis and equilibrium dialysis techniques. The results showed that the
interaction of mitoxantrone with SE-chromatin proceeds into compaction/aggregation as revealed by reduction in the absorbencies
at 608 and 260 nm (hypochromicity) and disappearance of both histones and DNA on the gels. Mitoxantrone interacts strongly
with histone proteins in solution making structural changes in the molecule as shown by CD and fluorescence analysis. The
binding isotherms demonstrate a positive cooperative binding pattern for the chromatin- mitoxantrone interaction. It is suggested
higher binding affinity of mitoxantrone to chromatin compared to DNA implying that the histone proteins may play an important
role in the chromatin- mitoxantrone interaction process. 相似文献
176.
Jeffrey E. McLean Emmanuel Datan Demetrius Matassov Zahra F. Zakeri 《Journal of virology》2009,83(16):8233-8246
The ectopic overexpression of Bcl-2 restricts both influenza A virus-induced apoptosis and influenza A virus replication in MDCK cells, thus suggesting a role for Bcl-2 family members during infection. Here we report that influenza A virus cannot establish an apoptotic response without functional Bax, a downstream target of Bcl-2, and that both Bax and Bak are directly involved in influenza A virus replication and virus-induced cell death. Bak is substantially downregulated during influenza A virus infection in MDCK cells, and the knockout of Bak in mouse embryonic fibroblasts yields a dramatic rise in the rate of apoptotic death and a corresponding increase in levels of virus replication, suggesting that Bak suppresses both apoptosis and the replication of virus and that the virus suppresses Bak. Bax, however, is activated and translocates from the cytosol to the mitochondria; this activation is required for the efficient induction of apoptosis and virus replication. The knockout of Bax in mouse embryonic fibroblasts blocks the induction of apoptosis, restricts the infection-mediated activation of executioner caspases, and inhibits virus propagation. Bax knockout cells still die but by an alternative death pathway displaying characteristics of autophagy, similarly to our previous observation that influenza A virus infection in the presence of a pancaspase inhibitor leads to an increase in levels of autophagy. The knockout of Bax causes a retention of influenza A virus NP within the nucleus. We conclude that the cell and virus struggle to control apoptosis and autophagy, as appropriately timed apoptosis is important for the replication of influenza A virus.The pathology of influenza A virus infection usually arises from acute lymphopenia and inflammation of the lungs and airway columnar epithelial cells (23, 38). Influenza A virus induces apoptotic death in infected epithelial, lymphocyte, and phagocytic cells, and apoptosis is a source of tissue damage during infection (3, 22, 33) and increased susceptibility to bacterial pathogens postinfection (31). While the induction of apoptosis by influenza A virus has been well documented (4, 19-21, 28, 33, 37), the mechanisms of this interaction are not well understood. Two viral proteins, NS1 and PB1-F2, have been associated with viral killing of cells. NS1, originally characterized as being proapoptotic (34), was later identified as being an interferon antagonist, inhibiting the activation of several key antiviral responses and restricting the apoptotic response to infection (1, 10, 15, 18, 35, 39, 46). In contrast, PB1-F2 induces apoptosis primarily by localizing to the outer mitochondrial membrane, promoting cytochrome c release, and triggering the apoptotic cascade (43). This effect, however, is typically restricted to infected monocytes, leading to the hypothesis that PB1-F2 induces apoptosis specifically to clear the landscape of immune responders (5, 44). Although PB1-F2 activity does not directly manipulate virus replication or virus-induced apoptosis, PB1-F2 localization to the mitochondrial membrane during infection potentiates the apoptotic response in epithelial and fibroblastic cells through tBID signaling with proapoptotic Bcl-2 family protein members Bax and Bak (22, 43, 44).The Bcl-2 protein family consists of both pro- and antiapoptotic members that regulate cytochrome c release during mitochondrion-mediated apoptosis through the formation of pore-like channels in the outer mitochondrial membrane (12, 16). During the initiation of mitochondrion-mediated apoptosis, cytoplasmic Bid is cleaved to form tBID. This, in turn, activates proapoptotic Bax and Bak (40), which drive cytochrome c release and subsequent caspase activation. Bak is constitutively associated with the mitochondrial membrane, whereas inactive Bax is primarily cytosolic, translocating to the outer mitochondrial membrane only after activation (6). The activation of Bax and Bak results in homo- and heterodimer formation at the outer mitochondrial membrane, generating pores that facilitate mitochondrial membrane permeabilization and cytochrome c release (14, 17), leading to caspase activation and the apoptotic cascade (8). Antiapoptotic members of the Bcl-2 protein family, including Bcl-2, inhibit the activation of proapoptotic Bax and Bak primarily by sequestering inactive Bax and Bak monomers via interactions between their BH3 homology domains (7).Bcl-2 expression has been linked to decreased viral replication rates (26). Bcl-2 overexpression inhibits influenza A virus-induced cell death and reduces the titer and spread of newly formed virions (29). The activation of caspase-3 in the absence of sufficient Bcl-2 is critical to the influenza A virus life cycle. Both Bcl-2 expression and the lack of caspase activation during infection lead to the nuclear accumulation of influenza virus ribonucleoprotein (RNP) complexes, thereby leading to the improper assembly of progeny virions and a marked reduction in titers of infectious virus (26, 41, 42, 45).Here we show that influenza A virus induces mitochondrion-mediated (intrinsic-pathway) apoptosis signaled specifically through Bax and that this Bax signaling is essential for the maximum efficiency of virus propagation. In contrast, Bak expression is strongly downregulated during infection. Cells lacking Bak (while expressing Bax) display a much more severe apoptotic phenotype in response to infection and produce infectious virions at a higher rate than the wild type (WT), suggesting that Bak, which can suppress viral replication, is potentially downregulated by the virus. Our results indicate essential and opposing roles for Bax and Bak in both the response of cells to influenza A virus infection and the ability of the virus to maximize its own replicative potential. 相似文献
177.
Plants synthesize an astonishing diversity of isoprenoids, some of which play essential roles in photosynthesis, respiration, and the regulation of growth and development. Two independent pathways for the biosynthesis of isoprenoid precursors coexist within the plant cell: the cytosolic mevalonic acid (MVA) pathway and the plastidial methylerythritol phosphate (MEP) pathway. However, little is known about the effects of plant hormones on the regulation of these pathways. In the present study we investigated the effect of gibberellic acid (GA3 ) on changes in the amounts of many produced terpenoids and the activity of the key enzymes, 1-deoxy-D-xylulose 5-phosphate synthase (DXS) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), in these pathways. Our results showed GA3 caused a decrease in DXS activity in both sexes that it was accompanied by a decrease in chlorophylls, carotenoids and Δ9 -tetrahydrocannabinol (THC) contents and an increase in α-tocopherol content. The treated plants with GA3 showed an increase in HMGR activity. This increase in HMGR activity was followed by accumulation of stigmasterol and β-sitosterol in male and female plants and campestrol in male plants. The pattern of the changes in the amounts of sterols was exactly similar to the changes in the HMGR activity. These data suggest that GA3 can probably influence the MEP and MVA pathways oppositely, with stimulatory and inhibitory effects on the produced primary terpenoids in MVA and DXS pathways, respectively. 相似文献
178.
Zahra Razaghi Moghadam Kashani Hayedeh Ahrabian Elahe Elahi Abbas Nowzari-Dalini Elnaz Saberi Ansari Sahar Asadi Shahin Mohammadi Falk Schreiber Ali Masoudi-Nejad 《BMC bioinformatics》2009,10(1):318
Background
Complex networks are studied across many fields of science and are particularly important to understand biological processes. Motifs in networks are small connected sub-graphs that occur significantly in higher frequencies than in random networks. They have recently gathered much attention as a useful concept to uncover structural design principles of complex networks. Existing algorithms for finding network motifs are extremely costly in CPU time and memory consumption and have practically restrictions on the size of motifs. 相似文献179.
Foroumadi A Kargar Z Sakhteman A Sharifzadeh Z Feyzmohammadi R Kazemi M Shafiee A 《Bioorganic & medicinal chemistry letters》2006,16(5):1164-1167
Two series of 2- and 3-[5-(nitroaryl)-1,3,4-thiadiazol-2-ylthio, sulfinyl and sulfonyl] propionic acid alkyl esters were synthesized and screened for antituberculosis activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. The MIC values for the compounds showing more than 90% inhibition were determined. The result of comparison between two groups of data exhibited that among the synthesized derivatives, the compound propyl 3-[5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-ylthio]propionate was the most active one (MIC=1.56 microgml(-1)). 相似文献
180.
MirAfzali Z Leipprandt JR McCracken JL DeWitt DL 《The Journal of biological chemistry》2006,281(38):28354-28364
The topology of association of the monotopic protein cyclooxygenase-2 (COX-2) with membranes has been examined using EPR spectroscopy of spin-labeled recombinant human COX-2. Twenty-four mutants, each containing a single free cysteine substituted for an amino acid in the COX-2 membrane binding domain were expressed using the baculovirus system and purified, then conjugated with a nitroxide spin label and reconstituted into liposomes. Determining the relative accessibility of the nitroxide-tagged amino acid side chains for the solubilized COX-2 mutants, or COX-2 reconstituted into liposomes to nonpolar (oxygen) and polar (NiEDDA or CrOx) paramagnetic reagents allowed us to map the topology of COX-2 interaction with the lipid bilayer. When spin-labeled COX-2 was reconstituted into liposomes, EPR power saturation curves showed that side chains for all but two of the 24 mutants tested had limited accessibility to both polar and nonpolar paramagnetic relaxation agents, indicating that COX-2 associates primarily with the interfacial membrane region near the glycerol backbone and phospholipid head groups. Two amino acids, Phe(66) and Leu(67), were readily accessible to the non-polar relaxation agent oxygen, and thus likely inserted into the hydrophobic core of the lipid bilayer. However these residues are co-linear with amino acids in the interfacial region, so their extension into the hydrophobic core must be relatively shallow. EPR and structural data suggest that membrane interaction of COX-2 is also aided by partitioning of 4 aromatic amino acids, Phe(59), Phe(66), Tyr(76), and Phe(84) to the interfacial region, and by the electrostatic interactions of two basic amino acids, Arg(62) and Lys(64), with the phospholipid head groups. 相似文献