全文获取类型
收费全文 | 30412篇 |
免费 | 2387篇 |
国内免费 | 2076篇 |
专业分类
34875篇 |
出版年
2024年 | 67篇 |
2023年 | 440篇 |
2022年 | 1018篇 |
2021年 | 1704篇 |
2020年 | 1040篇 |
2019年 | 1341篇 |
2018年 | 1279篇 |
2017年 | 930篇 |
2016年 | 1271篇 |
2015年 | 1856篇 |
2014年 | 2209篇 |
2013年 | 2476篇 |
2012年 | 2778篇 |
2011年 | 2465篇 |
2010年 | 1487篇 |
2009年 | 1281篇 |
2008年 | 1516篇 |
2007年 | 1321篇 |
2006年 | 1156篇 |
2005年 | 943篇 |
2004年 | 795篇 |
2003年 | 664篇 |
2002年 | 595篇 |
2001年 | 535篇 |
2000年 | 471篇 |
1999年 | 483篇 |
1998年 | 269篇 |
1997年 | 291篇 |
1996年 | 292篇 |
1995年 | 282篇 |
1994年 | 253篇 |
1993年 | 179篇 |
1992年 | 276篇 |
1991年 | 185篇 |
1990年 | 151篇 |
1989年 | 151篇 |
1988年 | 92篇 |
1987年 | 85篇 |
1986年 | 60篇 |
1985年 | 68篇 |
1984年 | 29篇 |
1983年 | 34篇 |
1982年 | 18篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 10篇 |
1975年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
Zhou L Liu Q Wang Q Ma Y Xu Y Yang Z Zhao Y Zhang Y 《Applied microbiology and biotechnology》2008,79(6):1027-1034
To synthesize and secrete heterologous proteins in an attenuated Vibrio anguillarum strain for potential multivalent live vaccine development, different antigen-delivery systems based on bacterial-originated secretion signal peptides (SPs) were designed and identified in this work. Four SPs were derived from hemolysin of Escherichia coli, RTX protein of V. cholerae, hemolysin of V. anguillarum, zinc-metalloprotease of V. anguillarum, respectively, and their abilities to support secretion of green fluorescent protein (GFP) in an attenuated V. anguillarum strain MVAV6203 were assayed. Immunodetection of GFP showed that the capability of the tested signal leaders to direct secretion of GFP varied greatly. Although all the four signal peptide-fused GFPs could be expressed correctly and trapped intracellularly in recombinant strains, only the EmpA signal peptide could confer efficient secretion to GFP. For the investigation of its potential application in live bacteria carrier vaccines, a heterologous protein EseB of Edwardsiella tarda was fused to the SP(empA) antigen-delivery system and introduced into the strain MVAV6203. Further analysis of EseB demonstrated that the constructed SP(empA) antigen-delivery system could be used to secrete foreign protein in attenuated V. anguillarum and be available for carrier vaccines development. 相似文献
72.
Manman Zhang Wenliang Gong Dianjun Zhang Ming Ji Binjie Chen Beina Chen Xinyu Li Yuefei Zhou Chengyi Dong Gehua Wen Xiaoni Zhan Xiafang Wu Lulu Cui Yuliang Feng Siman Wang Huiya Yuan Enyu Xu Maosheng Xia Alexei Verkhratsky Baoman Li 《Cell death & disease》2022,13(4)
Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.Subject terms: Cognitive neuroscience, Alzheimer''s disease, Cellular neuroscience 相似文献
73.
74.
75.
Volff JN Körting C Froschauer A Zhou Q Wilde B Schultheis C Selz Y Sweeney K Duschl J Wichert K Altschmied J Schartl M 《Genomics》2003,82(4):470-479
The Xmrk oncogene involved in melanoma formation in the fish Xiphophorus was formed relatively recently by duplication of the epidermal growth factor co-orthologue egfrb. In the platyfish X. maculatus, Xmrk is located close to the major sex-determining locus in a subtelomeric region of the X and Y sex chromosomes that frequently undergoes duplications and other rearrangements. This region accumulates repetitive sequences: more than 80% of the 33-kb region 3' of Xmrk is constituted by retrotransposable elements. The high degree of nucleotide identity between X- and Y-linked sequences and the rarity of gonosome-specific rearrangements indicated that the instability observed was not a manifestation of gonosome-specific degeneration. Seven other duplicated genes were found, all corresponding, in contrast to Xmrk, to pseudogenes (nonfunctionalization). Functional persistence of Xmrk in a highly unstable region in divergent Xiphophorus species suggests a beneficial function under certain conditions for this dispensable and potentially injurious gene. 相似文献
76.
77.
Deng C Wang J Zou Y Zhao Q Feng J Fu Z Guo C 《Journal of applied physiology (Bethesda, Md. : 1985)》2011,111(1):285-294
We sought to determine whether the extrapulmonary origin of fibroblasts derived from bone marrow (BM) progenitor cells is essential to lung fibrosis in bronchopulmonary dysplasia (BPD). Neonate mice were durably engrafted with BM isolated from transgenic reporter mice that expressed green fluorescent protein (GFP). Such chimera mice were subjected to 60% O(2) exposure for 14 days. A large number of fibroblast-specific protein-1 (FSP1) and GFP-positive fibroblasts were identified in active fibrotic lesions. More surprisingly, however, FSP1(+) fibroblasts also arose in considerable numbers from BM-derived alveolar type II cells (AT2) through epithelial-mesenchymal transition (EMT) during lung fibrogenesis. Cultured lung fibroblasts could express the CXC chemokine receptor (CXCR4) and responded chemotactically to their cognate ligand, chemokine (C-X-C motif) ligand 12 (CXCL12), which were elevated in the serum of BPD mice. These data suggest that lung fibroblasts in BPD fibrosis could variably arise from BM progenitor cells. This finding, which suggests the pathophysiological process of fibrosis, could contribute to a therapy for BPD that is characterized by extensive interstitial fibrosis. 相似文献
78.
Dun X Zhou Z Xia S Wen J Yi B Shen J Ma C Tu J Fu T 《The Plant journal : for cell and molecular biology》2011,68(3):532-545
Here, we describe the characteristics of a Brassica napus male sterile mutant 7365A with loss of the BnMs3 gene, which exhibits abnormal enlargement of the tapetal cells during meiosis. Later in development, the absence of the BnMs3 gene in the mutant results in a loss of the secretory function of the tapetum, as suggested by abortive callose dissolution and retarded tapetal degradation. The BnaC.Tic40 gene (equivalent to BnMs3) was isolated by a map-based cloning approach and was confirmed by genetic complementation. Sequence analyses suggested that BnaC.Tic40 originated from BolC.Tic40 on the Brassica oleracea linkage group C9, whereas its allele Bnms3 was derived from BraA.Tic40 on the Brassica rapa linkage group A10. The BnaC.Tic40 gene is highly expressed in the tapetum and encodes a putative plastid inner envelope membrane translocon, Tic40, which is localized into the chloroplast. Transmission electron microscopy (TEM) and lipid staining analyses suggested that BnaC.Tic40 is a key factor in controlling lipid accumulation in the tapetal plastids. These data indicate that BnaC.Tic40 participates in specific protein translocation across the inner envelope membrane in the tapetal plastid, which is required for tapetal development and function. 相似文献
79.
Xiaojin Liu Yan Wu Yanchun Zhou Liangming Zeng Tian Huang 《Biochemical and biophysical research communications》2009,386(1):181-185
Interleukin (IL)-33 is a recently described member of the IL-1 family and has been shown to induce production of T helper type 2 cytokines. In this study, an anti-IL-33 antibody was evaluated against pulmonary inflammation in mice sensitized and challenged with ovalbumin. The anti-IL-33 or a control antibody (150 μg/mouse) was given intraperitoneally as five doses before the sensitization and antigen challenge. Treatment with anti-IL-33 significantly reduced serum IgE secretion, the numbers of eosinophils and lymphocytes, and concentrations of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid compared with administration of a control antibody. Histological examination of lung tissue demonstrated that anti-IL-33 significantly inhibited allergen-induced lung eosinophilic inflammation and mucus hypersecretion. Our data demonstrate for the first time that anti-IL-33 antibody can prevent the development of asthma in a mouse model and indicate that blockade of IL-33 may be a new therapeutic strategy for allergic asthma. 相似文献
80.
The associations between E-cadherin (CDH1) gene polymorphisms and gastric cancer (GC) susceptibility are still controversial. Given this uncertainty, we carried out a meta-analysis of published case-control studies to derive more precise estimations of these relationships. Relevant studies were identified from PubMed and EMBASE up to March 2011. Seventeen studies with 3511 GC cases and 4826 controls were selected. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to investigate the strength of the associations. No associations between CDH1 (+54T>C, -160C>A, -347G>GA, -616G>C, -2076C>T and -3159T>C) gene polymorphisms and GC risk for all genetic models were found. As for CDH1 -160C>A polymorphism, subgroup analyses by country, gender, study design, smoking status, Helicobacter pylori infection, and the Lauren classification of GC did not change the results. When stratified by ethnicity, we found the A allele carriers had a significantly increased risk of GC among Caucasians (AA vs. CA+CC: OR=1.50, 95% CI=1.03-2.19, P=0.03), but not among Asians (AA vs. CA+CC: OR=0.87, 95% CI=0.56-1.37, P=0.56). No publication bias was found in the present study. This meta-analysis suggests that CDH1 -160C>A gene polymorphism may contribute to increased risk of GC among Caucasians. 相似文献