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891.
892.
High affinity, retinoid-specific binding proteins chaperone retinoids to manage their transport and metabolism. Proposing mechanisms of retinoid transfer between these binding proteins and membrane-associated retinoid-metabolizing enzymes requires insight into enzyme topology. We therefore determined the topology of mouse retinol dehydrogenase type 1 (Rdh1) and cis-retinoid androgen dehydrogenase type 1 (Crad1) in the endoplasmic reticulum of intact mammalian cells. The properties of Rdh1 were compared with a chimera with a luminal signaling sequence (11beta-hydroxysteroid dehydrogenase (11beta-HSD1)(1-41)/Rdh1(23-317); the green fluorescent protein (GFP) fusion proteins Rdh1(1-22)/GFP, Crad1(1-22)/GFP, and 11beta-HSD1(1-41)/GFP; and signaling sequence charge difference mutants using confocal immunofluorescence, antibody access, proteinase K sensitivity, and deglycosylation assays. An N-terminal signaling sequence of 22 residues, consisting of a hydrophobic helix ending in a net positive charge, anchors Rdh1 and Crad1 in the endoplasmic reticulum facing the cytoplasm. Mutating arginine to glutamine in the signaling sequence did not affect topology. Inserting one or two arginine residues near the N terminus of the signaling sequence caused 28-95% inversion from cytoplasmic to luminal, depending on the net positive charge remaining at the C terminus of the signaling sequence; e.g. the mutant L3R,L5R,R16Q,R19Q,R21Q faced the lumen. Experiments with N- and C-terminal epitope-tagged Rdh1 and molecular modeling indicated that a hydrophobic helix-turn-helix near the C terminus of Rdh1 (residues 289-311) projects into the cytoplasm. These data provide insight into the features necessary to orient type III (reverse signal-anchor) proteins and demonstrate that Rdh1, Crad1, and other short-chain dehydrogenases/reductases, which share similar N-terminal signaling sequences such as human Rdh5 and mouse Rdh4, orient with their catalytic domains facing the cytoplasm. 相似文献
893.
Nervous system tumors are one of the leading causes of cancer related death. Specific mechanisms facilitating the invasive
behavior of gliomas remain obscure. Advanced simulation models of the in vivo response to therapy conditions should potentially
improve malignant glioma treatment. Expressional profiling of vimentin––one of reliable pro-invasive tumor makers––in those
simulation models was the goal of this study, in order to estimate a pro-invasive response of surviving malignant glioma cells
under clinically relevant therapeutic conditions. Human U87-MG malignant glioma cells were used. These cells are characterized
by the wild p53-phenotype, which is relevant for the majority of primary malignant glioblastomas. Experimental design foresaw the cells to
undergo either irradiation or chemo-treatment with temozolomide alone, or combined treatment. Expression profiling of vimentin
was performed by quantitative “Real-Time”-PCR under all treatment conditions simulating diverse tumor regions. Here we demonstrated
that vimentin expression patterns in human malignant glioma cells strongly depend on cellular density, algorithms of drug
delivery and chemo/radio treatment. Substantial differences were recognized between immediate and late therapy effects. Significant
increase in vimentin expression levels was detected particularly in low-density cell cultures under durable treatment with
constant concentration levels of temezolomide. Simulation of variable intratumoral regional conditions (central intratumoral
regions vs. disseminated malignant cells in peripheral regions) demonstrated differential response of vimentin expression
in malignant glioma cell cultures treated under clinically relevant conditions. Slight ebbing of expression levels as late
effects of the treatment in confluent cultures may correspond to necrotic processes clinically observed in central intratumoral
regions. Contrary, in disseminated malignant cells of peripheral regions therapy resulted in vimentin-inducing effects. This
is in agreement with the clinical observations of an increased aggressiveness and malignancy grade of post-operatively chemo/radio-treated
malignant gliomas. 相似文献
894.
895.
Dawei Jiang Yunchao Liu Aiping Wang Gaiping Zhang Guoyu Yang Yumei Chen Pengchao Ji Chang Liu Yapeng Song Yunfang Su Guoqiang Wang Jucai Wang Baolei Zhao Ruiguang Deng 《Biotechnology letters》2016,38(6):901-908
Objectives
To improve the expression of soluble IBDV VP2 protein by using different tagged vectors in Escherichia coli.Results
Fusion tags, Grifin, MBP, SUMO, thioredoxin, γ-crystallin, ArsC and PpiB, enhanced the expression and solubility of VP2 protein. The fusion proteins were purified by Ni–NTA chromatography, MBP-VP2 showed the highest purity about 90 %. After removing the MBP tag, VP2 self-assembled into virus-like particles, ~25 nm diam. Results from AGP suggested the recombinant IBDV VP2 protein identified by reference serum like IBDV.Conclusion
All the seven tags enhanced the expression and solubility of IBDV VP2 protein. The recombinant protein self-assembly into virus like particles and possess antigenicity as reference IBDV.896.
Yuhan Lin Penglin Xia Fangyu Cao Cheng Zhang Yajie Yang Haitao Jiang Haishan Lin Hu Liu Ruling Liu Xiaodong Liu Jianming Cai 《Journal of cellular and molecular medicine》2023,27(2):246
Radiation‐induced intestinal injury (RIII) is a common complication after radiation therapy in patients with pelvic, abdominal, or retroperitoneal tumours. Recently, in the model of DSS (Dextran Sulfate Sodium Salt) ‐induced intestinal inflammatory injury, it has been found in the study that transgenic mice expressing hVDR in IEC (Intestinal Epithelial Cell) manifest highly anti‐injury properties in colitis, suggesting that activated VDR in the epithelial cells of intestine may inhibit colitis by protecting the mucosal epithelial barrier. In this study, we investigated the effect of the expression and regulation of VDR on the protection of RIII, and the radiosensitivity in vitro experiments, and explored the initial mechanism of VDR in regulating radiosensitivity of IEC. As a result, we found that the expression of VDR in intestinal tissues and cells in mice can be induced by ionizing radiation. VDR agonists are able to prolong the average survival time of mice after radiation and reduce the radiation‐induced intestinal injury. For lack of vitamin D, the radiosensitivity of intestinal epithelial cells in mice increased, which can be reduced by VDR activation. Ensuing VDR activation, the radiation‐induced intestinal stem cells damage is decreased, and the regeneration and differentiation of intestinal stem cells is promoted as well. Finally, on the basis of sequencing analysis, we validated and found that VDR may target the HIF/PDK1 pathway to mitigate RIII. We concluded that agonism or upregulation of VDR expression attenuates radiation‐induced intestinal damage in mice and promotes the repair of epithelial damage in intestinal stem cells. 相似文献
897.
Santos ME das C L E Silva F Gomes KB Fernandes AP Freitas FR Faria MC Mota AP Carvalho MG 《Molecular biology reports》2011,38(5):3361-3366
Peripheral arterial disease (PAD) is an atherosclerotic disturbance characterized by a progressive obstruction of lower limb
arteries. Many risk factors associated with PAD development have being reported in the literature. The present study aimed
to investigate whether mutations in the methylenetetrahydrofolate reductase (MTHFR) or in the cystathionine beta synthase
(CBS) genes are associated with higher levels of homocysteine and the risk of PAD in patients from Brazil. This study analyzed
39 patients with PAD and 32 without PAD in whom risk factors and C677T mutations in the MTHFR gene and both 844ins68 and T833C
mutations in the CBS gene were investigated. Although higher levels of homocysteine could be observed in patients with PAD
compared to controls, no association between the increase of homocysteine and the frequency of C677T, 844ins68, and T833C
mutations could be observed. The results suggest that these mutations do not appear to be related to either homocysteine levels
or the development of the disease. However, hyperhomocysteinemia and smoking are important factors in PAD development. 相似文献
898.
Naoki Kamada Kaori Tano Akiko Oyabu Yoshio Imura Naoko Narita Yasura Tashiro Atsuko Uchida Yoshihiro Komada Masaaki Narita 《International journal of peptide research and therapeutics》2010,16(2):55-61
We recently identified a novel 40-amino acid neuropeptide designated manserin from the rat brain (Yajima in NeuroReport 15:
1755–1759, 2004). Manserin is highly expressed in pituitary and hypothalamic nuclei, which suggests that it plays a role in
the endocrine system. In this study, we employed immunohistochemical methods to investigate the presence of manserin in rat
adrenal glands, as well as its regulation by physical stress. Immunohistochemical analysis using anti-manserin antibody showed
that manserin is present in the rat adrenal medulla but not in the cortex. When the colocalization of manserin and phenylethanolamine
N-methyltransferase (PNMT), an epinephrine-synthesizing enzyme, was examined, virtually all PNMT-positive cells expressed manserin.
Interestingly, the immunoreactivity of manserin was significantly increased when the rats were exposed to water-immersion
restraint stress. These results demonstrate for the first time that adrenal manserin, a novel neuropeptide, may have a potential
physiological role under stress-inducing conditions. 相似文献
899.
Fajar Adi-Kusumo 《Bulletin of mathematical biology》2017,79(6):1412-1425
We consider the dynamics of an influenza model with antigenic drift mechanism. Antigenic drift is an antigen mutation on the skin surface of the influenza virus that do not produce a new virus strain. The mutation produces the same virus but with slightly different antigens that cannot be recognized by the immune receptors formed by the previous infection. There are some type of influenza that involve the interaction between two populations such as human and animal. In this paper, we construct an influenza model with antigenic drift mechanism on the human population that has interaction with the animal population. The animal population is assumed to follow the SEIR epidemic model. Our model is motivated by the fact that some of the influenza cases in human come from the animal such as the swine and the avian. The transmission parameter that shows number of contact between the susceptible human and the infectious animals are important to study. The parameter plays an important role to detect the cycle of infection of the disease. The other important parameters are the seasonality degree, which shows the pathogen appearance and disappearance via annual migration, and the infection rate on the human population. We employ the bifurcation theory to analyze the behavior of the system and to detect the cycle of infection types when the parameters values are varied. 相似文献
900.
Meng F Han Y Teng W Li Y Li W 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(8):1459-1465
Soybean aphid (Aphis glycines Matsumura) results in severe yield loss of soybean in many soybean-growing countries of the world. A few loci have been previously
identified to be associated with the aphid resistance in soybean. However, none of them was via isoflavone-mediated antibiosis
process. The aim of the present study was to conduct genetic analysis of aphid resistance and to identify quantitative trait
loci (QTL) underlying aphid resistance in a Chinese soybean cultivar with high isoflavone content. One hundred and thirty
F5:6 derived recombinant inbred lines from the ‘Zhongdou 27’ × ‘Jiunong 20’ cross were used. Two QTL were directly associated
with resistance to aphid as measured by aphid damage index. qRa_1, close to Satt470 on soybean linkage group (LG) A2 (chromosome
8), was consistently detected for 3- and 4-week ratings and explained a large portion of phenotypic variations ranging from
25 to 35%. qRa_2, close to Satt144 of LG F (chromosome 13), was detected for 3- and 4-week ratings and could explain 7 and
11% of the phenotypic variation, respectively. These two QTL were highly associated with high isoflavone content and both
positive alleles were derived from ‘Zhongdou 27’, a cultivar with higher isoflavone content. The results revealed that higher
individual or total isoflavones contents in soybean lines could protect soybean against aphid attack. These two QTL detected
jointly provide potential for marker-assisted selection to improve the resistance of soybean cultivars to aphid along with
the increase of isoflavone content. 相似文献