全文获取类型
收费全文 | 10940篇 |
免费 | 1217篇 |
国内免费 | 1304篇 |
专业分类
13461篇 |
出版年
2024年 | 29篇 |
2023年 | 143篇 |
2022年 | 379篇 |
2021年 | 545篇 |
2020年 | 476篇 |
2019年 | 518篇 |
2018年 | 536篇 |
2017年 | 413篇 |
2016年 | 515篇 |
2015年 | 708篇 |
2014年 | 834篇 |
2013年 | 829篇 |
2012年 | 994篇 |
2011年 | 883篇 |
2010年 | 617篇 |
2009年 | 507篇 |
2008年 | 608篇 |
2007年 | 516篇 |
2006年 | 481篇 |
2005年 | 368篇 |
2004年 | 375篇 |
2003年 | 374篇 |
2002年 | 365篇 |
2001年 | 250篇 |
2000年 | 165篇 |
1999年 | 185篇 |
1998年 | 108篇 |
1997年 | 94篇 |
1996年 | 90篇 |
1995年 | 96篇 |
1994年 | 68篇 |
1993年 | 56篇 |
1992年 | 54篇 |
1991年 | 46篇 |
1990年 | 40篇 |
1989年 | 44篇 |
1988年 | 26篇 |
1987年 | 20篇 |
1986年 | 18篇 |
1985年 | 8篇 |
1984年 | 12篇 |
1983年 | 14篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1974年 | 2篇 |
1972年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
61.
Epidermal growth factor receptor and notch pathways participate in the tumor suppressor function of gamma-secretase 总被引:1,自引:0,他引:1
Li T Wen H Brayton C Das P Smithson LA Fauq A Fan X Crain BJ Price DL Golde TE Eberhart CG Wong PC 《The Journal of biological chemistry》2007,282(44):32264-32273
Gamma-secretase, a unique aspartyl protease, is required for the regulated intramembrane proteolysis of Notch and APP, pathways that are implicated, respectively, in the pathogenesis of cancer and Alzheimer disease. However, the mechanism whereby reduction of gamma-secretase causes tumors such as squamous cell carcinoma (SCC) remains poorly understood. Here, we demonstrate that gamma-secretase functions in epithelia as a tumor suppressor in an enzyme activity-dependent manner. Notch signaling is down-regulated and epidermal growth factor receptor (EGFR) is activated in SCC caused by genetic reduction of gamma-secretase. Moreover, the level of EGFR is inversely correlated with the level of gamma-secretase in fibroblasts, suggesting that the up-regulation of EGFR stimulates hyperproliferation in epithelia of mice with genetic reduction of gamma-secretase. Supporting this notion is our finding that the proliferative response of fibroblasts lacking gamma-secretase activity is more sensitive when challenged by either EGF or an inhibitor of EGFR as ompared with wild type cells. Interestingly, the up-regulation of EGFR is independent of Notch signaling, suggesting that the EGFR pathway functions in parallel with Notch in the tumorigenesis of SCC. Collectively, our results establish a novel mechanism linking the EGFR pathway to the tumor suppressor role of gamma-secretase and that mice with genetic reduction of gamma-secretase represent an excellent rodent model for clarifying pathogenesis of SCC and for testing therapeutic strategy to ameliorate this type of human cancer. 相似文献
62.
Carbon accumulation and distribution in Pinus massoniana and Cunninghamia lanceolata mixed forest ecosystem in Daqingshan, Guangxi, China 总被引:1,自引:0,他引:1 下载免费PDF全文
Carbon accumulation and distribution were studied at three sampling plots in a 13-year-old mixed planatation of Pinus massoniana and Cunninghamia lanceolata in Daqingshan, Guangxi, China. The results showed that carbon content varied with tissues and tree species, but the total carbon content of Pinus massoniana was higher than that of Cunninghamia lanceolata. The average tissue carbon contents of Pinus massoniana were: wood (58.6%) > root (56.3%) > branch (51.2%) > bark (49.8%) > leaf (46.8%), while those of Cunninghamia lanceolata were: bark (52.2%) > leaf (51.8%) > wood (50.2%) > root (47.5%) > branch (46.7%). The carbon contents of the soil (at a depth of 60cm) ranged from 1.45% to 1.84% with an average of 1.70%. Carbon contents were higher in the surface soil (0–20cm) than in the deep layer (below 20cm). The average carbon contents were the highest for trees (51.1%), followed by litter (48.3%), shrubs (44.1%), and herbs (33.0%). The biomass of the trees in the three plots ranged from 85.35 t hm-2 to 101.35 t hm-2 with an average of 93.83 t hm-2, in which 75.7%–82.6% was Pinus massoniana. The biomass of the understory was 2.10–3.95 t hm-2 with an average of 2.72 t hm-2, while the standing stock of ground litter was 5.49–7.91 t hm-2 with an average of 6.75 t hm-2. The carbon storage in the mixed plantation reached the maximum in the soil layer (69.02%), followed by vegetation (29.03%), and standing litter (1.82%). The carbon storage in the tree layer occupied 23.90% of the total ecosystem and 97.7% of the vegetation layer. Pinus massoniana accounted for 65.39% of the total carbon storage in the tree layer. Tissue carbon storage was directly related to the corresponding amount of biomass. Trunks had the highest carbon storage, accounting for 53.23% of the trees in Pinus massoniana and 55.57% in Cunninghamia lanceolata, respectively. Roots accounted for about 19.22% of the total tree carbon. The annual net productivity of the mixed plantation was 11.46 t hm-2a-1, and that of sequestered carbon was 5.96 t hm-2a-1, which was equivalent to fixing CO2 of 21.88 t hm-2a-1. The plantation was found to be an important sink of atmospheric CO2. 相似文献
63.
Ya‐Yun Zuo Huan‐Huan Ma Wen‐Jie Lu Xing‐Liang Wang Shu‐Wen Wu Ralf Nauen Yi‐Dong Wu Yi‐Hua Yang 《Insect Science》2020,27(4):791-800
Insect ryanodine receptors (RyRs) are the targets of diamide insecticides. Two point mutations G4946E and I4790M (numbering according to Plutella xylostella, PxRyR) in the transmembrane domain of the insect RyRs associated with diamide resistance have so far been identified in three lepidopteran pests, P. xylostella, Tuta absoluta and Chilo suppressalis. In this study, we identified one of the known RyR target site resistance mutations (I4790M) in a field‐collected population of Spodoptera exigua. The field‐collected WF population of S. exigua exhibited 154 fold resistance to chlorantraniliprole when compared with the susceptible WH‐S strain. Sequencing the transmembrane domains of S. exigua RyR (SeRyR) revealed that the resistant WF strain was homozygous for the I4743M mutation (corresponding to I4790M in PxRyR), whereas the G4900E allele (corresponding to G4946E of PxRyR) was not detected. The 4743M allele was introgressed into the susceptible WH‐S strain by crossing WF with WH‐S, followed by three rounds of backcrossing with WH‐S. The introgressed strain 4743M was homozygous for the mutant 4743M allele and shared about 94% of its genetic background with that of the recipient WH‐S strain. Compared with WH‐S, the near‐isogenic 4743M strain showed moderate levels of resistance to chlorantraniliprole (21 fold), cyantraniliprole (25 fold) and flubendiamide (22 fold), suggesting that the I4743M mutation confers medium levels of resistance to all three diamides. Genetic analysis showed diamide resistance in the 4743M strain was inherited as an autosomal and recessive trait. Results from this study have direct implications for the design of appropriate resistance monitoring and management practices to sustainably control S. exigua. 相似文献
64.
Changchun Cao Xiaoyan Dong Xiaobing Wu Boyun Wen Gang Ji Lingpeng Cheng Hongrong Liu 《Journal of virology》2012,86(22):12322-12329
Adenovirus (Ad) cell attachment is initiated by the attachment of the fiber protein to a primary receptor (usually CAR or CD46). This event is followed by the engagement of the penton base protein with a secondary receptor (integrin) via its loop region, which contains an Arg-Gly-Asp (RGD) motif, to trigger virus internalization. To understand the well-orchestrated adenovirus cell attachment process that involves the fiber and the penton base, we reconstructed the structure of an Ad5F35 capsid, comprising an adenovirus type 5 (Ad5) capsid pseudotyped with an Ad35 fiber, at a resolution of approximately 4.2 Å. The fiber-penton base interaction in the cryo-electron microscopic (cryo-EM) structure of Ad5F35 is similar to that in the cryo-EM structure of Ad5, indicating that the fiber-penton base interaction of adenovirus is conserved. Our structure also confirms that the C-terminal segment of the fiber tail domain constitutes the bottom trunk of the fiber shaft. Based on the conserved fiber-penton base interaction, we have proposed a model for the interaction of Ad5F35 with its primary and secondary receptors. This model could provide insight for designing adenovirus gene delivery vectors. 相似文献
65.
66.
67.
H Gross C Hennard I Masouris C Cassel S Barth U Stober-Grässer A Mamiani B Moritz D Ostareck A Ostareck-Lederer N Neuenkirchen U Fischer W Deng H Leonhardt E Noessner E Kremmer FA Grässer 《PloS one》2012,7(8):e42106
The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2) Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K). Specific binding of the ADMA- antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV- infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties. 相似文献
68.
69.
Shi Yang Li Wei Yu Yao Yong Jin Yuan Wen Shu Tay Nian-Lin Reena Han Rehena Sultana Pryseley N. Assam Alex Tiong-Heng Sia Ban Leong Sng 《BMC anesthesiology》2017,17(1):169
Background
The Supreme? laryngeal mask airway (SLMA) is a single-use LMA with double lumen design that allows separation of the respiratory and the alimentary tract, hence potentially reducing the gastric volume and risk of aspiration. The purpose of this prospective cohort study is to evaluate the the role of the SLMA as an airway technique for women undergoing category 2 and 3 Cesarean delivery under general anesthesia.Methods
We recruited 584 parturients who underwent category 2 or 3 Cesarean delivery under general anesthesia, in which 193 parturients underwent category 2 and 391 parturients underwent category 3 Cesarean delivery. The primary outcome was insertion success rate at 1st attempt in SLMA insertion. The secondary outcomes included anaesthetic, obstetric outcomes and maternal side effects associated with airway device.Results
The 1st attempt insertion success rate was 98.3%, while the overall insertion success rate was 100%. The mean (Standard deviation) time to effective ventilation was 15.6 (4.4) seconds. Orogastric tube insertion was successful at the 1st attempt in all parturients. There was no clinical evidence of aspiration or regurgitation. No episodes of hypoxemia, laryngospasm or bronchospasm were observed intra-operatively. The incidence of complications was low and with good maternal satisfaction reported.Conclusions
The SLMA could be an alternative effective airway in category 2 and 3 parturients emergency Cesarean Delivery under general anesthesia in a carefully-selected obstetric population.Trial registration
Clinical Trials Registration: Clinicaltrials.gov Registration NCT02026882. Registered on December 31, 2013.70.
The rhizospheric bacterium JW-SD2 was identified as Pseudomonas frederiksbergensis based on phenotypic features, the Biolog Identification System and 16S rRNA sequence analysis. The phosphate-solubilizing activity, acidification in culture media, growth rate and organic acid secretion of JW-SD2 were investigated during 192 h of cultivation. The phosphate solubilized by JW-SD2 reached 7.75 mM. The decrease of pH and increase of titratable acidity were closely correlated (Pearson’s r?=??0.953 and 0.969, respectively) with the phosphate-solubilizing activity. High concentrations of gluconic, 2-ketogluconic, pyruvic, maleic and malic acids were detected before 96 h of culture, when the strain displayed a high level of phosphate-solubilizing activity, indicating that these organic acids were efficient components in phosphate solubilization. However, acetic acid did not affect phosphate solubilization as shown by a remarkable increase at 144 h of culture when the phosphate-solubilizing activity decreased. The phosphate-solubilizing ability of JW-SD2 was significantly (P?<?0.01) affected by environmental factors. Over a broad ranges of temperature (20?35 °C), pH (4?9), salinity (0?3.0 %), and volume of medium (1/5?3/5 of flask volume), the phosphate solubilized by JW-SD2 remained above 4.00 mM, demonstrating good potential in adapting to a changing environment. The inoculation experiments indicated that JW-SD2 could significantly (P?<?0.05) promote growth of poplar (Populus euramericana cv. NL-895) in both sterilized and non-sterilized soils. The effects of plant growth promotion were greater in non-sterilized than in sterilized soil. During the 150 days of the trial, the effects of plant growth promotion by JW-SD2 first increased then decreased over time, suggesting that, in field applications, the periodic supplementation of the strain into the rhizosphere should be considered. 相似文献