全文获取类型
收费全文 | 1548篇 |
免费 | 154篇 |
国内免费 | 2篇 |
出版年
2023年 | 12篇 |
2022年 | 10篇 |
2021年 | 69篇 |
2020年 | 31篇 |
2019年 | 35篇 |
2018年 | 50篇 |
2017年 | 44篇 |
2016年 | 59篇 |
2015年 | 97篇 |
2014年 | 105篇 |
2013年 | 114篇 |
2012年 | 153篇 |
2011年 | 143篇 |
2010年 | 91篇 |
2009年 | 76篇 |
2008年 | 83篇 |
2007年 | 83篇 |
2006年 | 72篇 |
2005年 | 69篇 |
2004年 | 52篇 |
2003年 | 39篇 |
2002年 | 44篇 |
2001年 | 7篇 |
1999年 | 5篇 |
1998年 | 13篇 |
1997年 | 9篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1984年 | 5篇 |
1982年 | 8篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1976年 | 6篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1965年 | 3篇 |
1964年 | 5篇 |
1961年 | 4篇 |
1960年 | 6篇 |
1930年 | 2篇 |
1902年 | 2篇 |
1899年 | 2篇 |
排序方式: 共有1704条查询结果,搜索用时 265 毫秒
101.
Verbout NG Lorton JK Jacoby DB Fryer AD 《American journal of physiology. Lung cellular and molecular physiology》2007,292(5):L1126-L1135
Airway hyperreactivity in antigen-challenged animals is mediated by eosinophil major basic protein (MBP) that blocks inhibitory M(2) muscarinic receptors on parasympathetic nerves, increasing acetylcholine release onto M(3) muscarinic receptors on airway smooth muscle. Acutely, anticholinergics block hyperreactivity in antigen-challenged animals and reverse asthma exacerbations in the human, but are less effective in chronic asthma. We tested whether atropine, given before antigen challenge, affected hyperreactivity, M(2) receptor function, eosinophil accumulation, and activation. Sensitized guinea pigs received atropine (1 mg/kg ip) 1 h before challenge and 6 h later. Twenty-four hours after challenge, animals were anesthetized, vagotomized, paralyzed, and ventilated. Airway reactivity to electrical stimulation of the vagi and to intravenous acetylcholine was not altered by atropine pretreatment in nonsensitized animals, indicating that atropine was no longer blocking postjunctional muscarinic receptors. Antigen challenge induced airway hyperreactivity to vagal stimulation that was significantly potentiated by atropine pretreatment. Bronchoconstriction induced by acetylcholine was not changed by antigen challenge or by atropine pretreatment. M(2) receptor function was lost in challenged animals but protected by atropine pretreatment. Eosinophils in bronchoalveolar lavage and within airway tissues were significantly increased by challenge but significantly reduced by atropine pretreatment. However, extracellular MBP in challenged airways was significantly increased by atropine pretreatment, which may account for reduced eosinophils. Depleting eosinophils with antibody to IL-5 before challenge prevented hyperreactivity and significantly reduced MBP in airways of atropine-pretreated animals. Thus atropine pretreatment potentiated airway hyperreactivity by increasing eosinophil activation and degranulation. These data suggest that anticholinergics enhance eosinophil interactions with airway nerves. 相似文献
102.
cGMP-dependent protein kinase I interacts with TRIM39R, a novel Rpp21 domain-containing TRIM protein
Roberts JD Chiche JD Kolpa EM Bloch DB Bloch KD 《American journal of physiology. Lung cellular and molecular physiology》2007,293(4):L903-L912
Nitric oxide modulates vascular smooth muscle cell (SMC) cytoskeletal kinetics and phenotype, in part, by stimulating cGMP-dependent protein kinase I (PKGI). To identify molecular targets of PKGI, an interaction trap screen in yeast was performed using a cDNA encoding the catalytic region of PKGI and a human lung cDNA library. We identified a cDNA that encodes a putative PKGI-interactor that is a novel variant of TRIM39, a member of the really interesting new gene (RING) finger family of proteins. Although this TRIM39 variant encodes the NH(2)-terminal RING finger (RF), B-box, and coiled-coil (RBBC) domains of TRIM39, instead of a complete COOH-terminal B30.2 domain, this TRIM39 isoform contains the COOH-terminal portion of Rpp21, a component of RNase P. RT-PCR demonstrated that the TRIM39 variant, which we refer to as TRIM39R, is transcribed in the human fetal lung and in rat pulmonary artery SMC. Indirect immunofluorescence using an antibody generated against the conserved domains of TRIM39 and TRIM39R revealed the proteins in speckled intranuclear structures in human acute monocytic leukemia (THP-1) and human epidermal carcinoma line (HEp-2) cells. PKGI phosphorylated a typical PKGI/PKA phosphorylation domain in a conserved region of TRIM39 and TRIM39R. Additional studies demonstrated that PKGI interacts with both isoforms of TRIM39 in yeast cells and phosphorylates both isoforms of TRIM39 in human cell lines. Although PKGI has been observed to interact with proteins that regulate cytoskeletal function and gene expression, this investigation shows for the first time that PKGI interacts with tripartite motif (TRIM) proteins, which, through diverse molecular pathways, are often observed to regulate important aspects of cellular homeostasis. 相似文献
103.
104.
Paraoxonases are associated with intestinal inflammatory diseases and intracellularly localized to the endoplasmic reticulum 总被引:2,自引:0,他引:2
Rothem L Hartman C Dahan A Lachter J Eliakim R Shamir R 《Free radical biology & medicine》2007,43(5):730-739
We demonstrated previously that the paraoxonase (PON1/2/3) genes and proteins are expressed in human intestinal biopsies and in Caco-2 cells. The current study aims were to explore whether PON1/2/3 expression is different in inflammatory bowel diseases (IBD) or celiac disease compared to healthy controls, and to explore the intracellular localization of PON1/2/3. Our results showed that significantly fewer biopsies expressed PON1 and PON3 in the duodenum of celiac patients (PON1, P<0.0001; PON3, P=0.03), in the terminal ileum of Crohn's patients (PON1, P=0.001; PON3, P=0.008), and in the colon of UC patients (PON1, P=0.02; PON3, P=0.06) compared to controls. Since all three disorders share markedly elevated inflammatory mediators we explored the PON1/2/3 mRNA expression on cytokine stimulation. No changes were observed in Caco-2 and HT29 cells. Immunofluorescence experiments localized PON1/2/3 exclusively to the endoplasmic reticulum (ER) in both CaCo-2 and HT29 cells. These results demonstrate for the first time a novel relationship between PON1 and PON3 expression and several inflammatory gastrointestinal disorders. Together with the localization of PON1/2/3 enzymes to the ER, it may be suggested that PON1/2/3 may have extracellular functions as part of the host response in IBD and celiac disease. 相似文献
105.
106.
tRNA‐dependent alanylation of diacylglycerol and phosphatidylglycerol in Corynebacterium glutamicum 下载免费PDF全文
Angela M. Smith Jesse S. Harrison Christopher D. Grube Austin E. F. Sheppe Nahoko Sahara Ryohei Ishii Osamu Nureki Hervé Roy 《Molecular microbiology》2015,98(4):681-693
Aminoacyl‐phosphatidylglycerol synthases (aaPGSs) are membrane proteins that utilize aminoacylated tRNAs to modify membrane lipids with amino acids. Aminoacylation of membrane lipids alters the biochemical properties of the cytoplasmic membrane and enables bacteria to adapt to changes in environmental conditions. aaPGSs utilize alanine, lysine and arginine as modifying amino acids, and the primary lipid recipients have heretofore been defined as phosphatidylglycerol (PG) and cardiolipin. Here we identify a new pathway for lipid aminoacylation, conserved in many Actinobacteria, which results in formation of Ala‐PG and a novel alanylated lipid, Alanyl‐diacylglycerol (Ala‐DAG). Ala‐DAG formation in Corynebacterium glutamicum is dependent on the activity of an aaPGS homolog, whereas formation of Ala‐PG requires the same enzyme acting in concert with a putative esterase encoded upstream. The presence of alanylated lipids is sufficient to enhance the bacterial fitness of C. glutamicum cultured in the presence of certain antimicrobial agents, and elucidation of this system expands the known repertoire of membrane lipids acting as substrates for amino acid modification in bacterial cells. 相似文献
107.
Symbiodinium transcriptome and global responses of cells to immediate changes in light intensity when grown under autotrophic or mixotrophic conditions 下载免费PDF全文
108.
109.
110.
Ting Wang Robert Grabski Elizabeth Sztul Jesse C. Hay 《Traffic (Copenhagen, Denmark)》2015,16(2):148-171
Tethering factors regulate the targeting of membrane‐enclosed vesicles under the control of Rab GTPases. p115, a golgin family tether, has been shown to participate in multiple stages of ER/Golgi transport. Despite extensive study, the mechanism of action of p115 is poorly understood. SNARE proteins make up the machinery for membrane fusion, and strong evidence shows that function of p115 is directly linked to its interaction with SNAREs. Using a gel filtration binding assay, we have demonstrated that in solution p115 stably interacts with ER/Golgi SNAREs rbet1 and sec22b, but not membrin and syntaxin 5. These binding preferences stemmed from selectivity of p115 for monomeric SNARE motifs as opposed to SNARE oligomers. Soluble monomeric rbet1 can compete off p115 from coat protein II (COPII) vesicles. Furthermore, excess p115 inhibits p115 function in trafficking. We conclude that monomeric SNAREs are a major binding site for p115 on COPII vesicles, and that p115 dissociates from its SNARE partners upon SNAREpin assembly. Our results suggest a model in which p115 forms a mixed p115/SNARE helix bundle with a monomeric SNARE, facilitates the binding activity and/or concentration of the SNARE at prefusion sites and is subsequently ejected as SNARE complex formation and fusion proceed. 相似文献