全文获取类型
收费全文 | 25530篇 |
免费 | 2108篇 |
国内免费 | 2103篇 |
专业分类
29741篇 |
出版年
2024年 | 66篇 |
2023年 | 351篇 |
2022年 | 803篇 |
2021年 | 1332篇 |
2020年 | 867篇 |
2019年 | 1057篇 |
2018年 | 1003篇 |
2017年 | 744篇 |
2016年 | 1056篇 |
2015年 | 1555篇 |
2014年 | 1834篇 |
2013年 | 1938篇 |
2012年 | 2363篇 |
2011年 | 2026篇 |
2010年 | 1283篇 |
2009年 | 1024篇 |
2008年 | 1396篇 |
2007年 | 1169篇 |
2006年 | 1054篇 |
2005年 | 898篇 |
2004年 | 745篇 |
2003年 | 636篇 |
2002年 | 580篇 |
2001年 | 490篇 |
2000年 | 378篇 |
1999年 | 430篇 |
1998年 | 258篇 |
1997年 | 218篇 |
1996年 | 256篇 |
1995年 | 206篇 |
1994年 | 252篇 |
1993年 | 152篇 |
1992年 | 221篇 |
1991年 | 184篇 |
1990年 | 174篇 |
1989年 | 113篇 |
1988年 | 83篇 |
1987年 | 75篇 |
1986年 | 49篇 |
1985年 | 63篇 |
1984年 | 48篇 |
1983年 | 39篇 |
1982年 | 37篇 |
1981年 | 24篇 |
1980年 | 16篇 |
1979年 | 25篇 |
1977年 | 15篇 |
1976年 | 16篇 |
1975年 | 15篇 |
1973年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
Small heat shock proteins (sHSPs) are the most diverse but also the most poorly known family of molecular chaperones, and they play essential roles in various biological processes. The striped stem borer, Chilo suppressalis (Insecta: Lepidoptera: Pyralidae), is one of the most serious pests of rice, causing extensive damage and yield loss. In this study, we isolated and characterized five members of the sHSPs family—Cshsp19.8, Cshsp21.4, Cshsp21.5, Cshsp21.7a, and Cshsp21.7b—from C. suppressalis. The cDNAs of these genes encoded proteins of 177, 187, 191, 191, and 191 amino acids with isoelectric points of 7.0, 5.6, 6.1, 6.3, and 6.3, respectively. While Cshsp19.8, Cshsp21.5, and Cshsp21.7b had no introns, Cshsp21.4 and Cshsp21.7a contained one and two introns, respectively. Structural analysis indicated that all five Cshsps possessed conserved arginine and a V/IXI/V motif, which is related to hydrophobic characteristics of sHSPs. The five heat shock proteins can be classified into two main groups: an orthologous type (Cshsp21.4 and Cshsp21.7a) and a species-specific type (Cshsp19.8, Cshsp21.5, and Cshsp21.7b). Real-time quantitative PCR analyses revealed that Cshsp19.8, Cshsp21.5, Cshsp21.7a, and Cshsp21.7b all exhibited their highest expression levels within Malpighian tubules or the hindgut, while such levels were found in the head for Cshsp21.4. The expression of Csshsps at different developmental stages revealed that the mRNA levels of Cshsp19.8, Cshsp21.4, Cshsp21.5, and Cshsp21.7b peaked in adults, whereas the highest level of Cshsp21.7a was observed in first instar larvae. Cshsp19.8 and Cshsp21.7b were both upregulated dramatically by heat and cold, and Cshsp21.5 could be induced by cold stress. Neither Cshsp21.4 nor Cshsp21.7a responded to heat or cold. These results demonstrated that different Csshsps play distinctive roles in the regulation of the physiological activities in C. suppressalis. 相似文献
993.
The Drosophila homolog of schizophrenia susceptibility gene dysbindin(Ddysb)affects a range of behaviors through regulation of multiple neurotransmitter signals,including dopamine activity.To gain insights into mechanisms underlying Ddysb-dependent regulation of dopamine signal,we investigated interaction between Ddysb and Ebony,the Drosophilaβ-alanyl-monoamine synthase involved in dopamine recycling.We found that Ddysb was capable of regulating expression of Ebony in a bi-directional manner and its subcellular distribution.Such regulation is confined to glial cells.The expression level of ebony and its accumulation in glial soma depend positively on Ddysb activity,whereas its distribution in glial processes is bound to be reduced in response to any alterations of Ddysb from the normal control level,either an increase or decrease.An optimal binding ratio between Dysb and Ebony might contribute to such non-linear effects.Thus,Ddysb-dependent regulation of Ebony could be one of the mechanisms that mediate dopamine signal. 相似文献
994.
995.
锥花莸 (CaryopterispaniculataB .C .Clarke)属莸属 (CaryopterisBunge)的假莸组 (Sect.PseudocaryopterisBriq .)。亚热带分布 ,产印度东北部、尼泊尔、不丹、缅甸北部、泰国 ,我国产云南东南、西南及南部 ,广西、四川、贵州也有分布。生长于海拔 6 50— 2 30 0m的常绿阔叶林、混交林、箐沟疏林下 ,也常见于林缘、路旁、石灰岩山、干草地以及荒地等群落中。莸属不仅系统位置存在争议 (Cantino ,1 992 ) ,且近年来孢粉学 (Mones等 ,1 993)、形态学 (… 相似文献
996.
Objective
To evaluate the performance of Finnish Diabetes Risk Score (FINDRISC) in detecting undiagnosed diabetes and prediabetes among U.S. adults by gender and race.Methods
This cross-sectional analysis included participants (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES) 1999–2010. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve and the optimal cutoff points for identifying undiagnosed diabetes and prediabetes were calculated for FINDRISC by gender and race/ethnicity.Results
Among the 20,633 adults (≥20 years), 49.8% were women and 53.0% were non-Hispanic White. The prevalence of undiagnosed diabetes and prediabetes was 4.1% and 35.6%, respectively. FINDRISC was positively associated with the prevalence of diabetes (OR = 1.48 for 1 unit increase, p<0.001) and prediabetes (OR = 1.15 for 1 unit increase, p<0.001). The area under ROC for detecting undiagnosed diabetes was 0.75 for total population, 0.74 for men and 0.78 for women (p = 0.04); 0.76 for White, 0.76 for Black and 0.72 for Hispanics (p = 0.03 for White vs. Hispanics). The area under ROC for detecting prediabetes was 0.67 for total population, 0.66 for men and 0.70 for women (p<0.001); 0.68 for White, 0.67 for Black and 0.65 for Hispanics (p<0.001 for White vs. Hispanics). The optimal cutoff point was 10 (sensitivity = 0.75) for men and 12 (sensitivity = 0.72) for women for detecting undiagnosed diabetes; 9 (sensitivity = 0.61) for men and 10 (sensitivity = 0.69) for women for detecting prediabetes.Conclusions
FINDRISC is a simple and non-invasive screening tool to identify individuals at high risk for diabetes in the U.S. adults. 相似文献997.
Lu Zhou Sun Jung Yoon Kyu Yun Jang Young Jae Moon Sajeev Wagle Kwang Bok Lee Byung-Hyun Park Jung Ryul Kim 《PloS one》2014,9(10)
Angiogenesis is considered essential for proper bone regeneration. The purpose of this investigation was to determine if a combined therapy of bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein angiopoietin-1 (COMP-Ang1) can potentiate the therapeutic effect of BMP-2 in a rat model of ischemic necrosis of the femoral head (INFH). INFH was surgically induced in the femoral head of rats, and the animals were divided into the following groups: 1) a sham-operated group (sham group), 2) a bovine serum albumin-injected group (BSA group), 3) a BMP-2-injected group (BMP-2 group), and 4) a COMP-Ang1 and BMP-2-injected group (COMP-Ang1 + BMP-2 group) (n = 20/group). Radiologic, histologic, and histomorphometric assessments were performed to assess femoral head morphology, vascular density, and bone resorption activity. Western blots and immunohistochemical staining were performed to evaluate production of BMP-related signaling proteins in C3H10T1/2 cells and tissues. Real-time RT-PCR was performed to investigate expression of the target integrin gene, and the effect of integrin on C3H10T1/2 cells was determined using a cell adhesion assay. Radiographs obtained six weeks after injection revealed better preservation of the architecture of the femoral head in the COMP-Ang1 + BMP-2 group compared with the BSA and BMP-2 groups. Histological findings indicated increased trabecular bone and vascularity and decreased osteoclast bone resorption activity in the COMP-Ang1 + BMP-2 group compared with those in the BSA and BMP-2 groups. The combination of COMP-Ang1 and BMP-2 increased phosphorylation of Smad1/3/5, p38, and Akt. Increased integrin α3 and β1 mRNA expression in the COMP-Ang1 + BMP-2 group promoted cell adhesion. These results suggest that COMP-Ang1 preserved the necrotic femoral head through the potentiation of BMP-2 signaling pathways and angiogenesis. Combination treatment with COMP-Ang1 and BMP-2 may be a clinically useful therapeutic application in INFH. 相似文献
998.
Wei Chen George Lewith Li-qiong Wang Jun Ren Wen-jing Xiong Fang Lu Jian-ping Liu 《PloS one》2014,9(10)
Objective
Chinese proprietary herbal medicines (CPHMs) have long history in China for the treatment of common cold, and lots of them have been listed in the ‘China national essential drug list’ by the Chinese Ministry of Health. The aim of this review is to provide a well-round clinical evidence assessment on the potential benefits and harms of CPHMs for common cold based on a systematic literature search to justify their clinical use and recommendation.Methods
We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites from their inception to 31 March 2013 for clinical studies of CPHMs listed in the ‘China national essential drug list’ for common cold. There was no restriction on study design.Results
A total of 33 CPHMs were listed in ‘China national essential drug list 2012’ for the treatment of common cold but only 7 had supportive clinical evidences. A total of 6 randomised controlled trials (RCTs) and 7 case series (CSs) were included; no other study design was identified. All studies were conducted in China and published in Chinese between 1995 and 2012. All included studies had poor study design and methodological quality, and were graded as very low quality.Conclusions
The use of CPHMs for common cold is not supported by robust evidence. Further rigorous well designed placebo-controlled, randomized trials are needed to substantiate the clinical claims made for CPHMs. 相似文献999.
Xia Zhao Shuangshuang Lu Junwei Nie Xiaoshan Hu Wen Luo Xiangqi Wu Hailang Liu Qiuting Feng Zai Chang Yaoqiu Liu Yunshan Cao Haixiang Sun Xinli Li Yali Hu Zhongzhou Yang 《Molecular and cellular biology》2014,34(11):1966-1975
The protein kinase Akt plays a critical role in heart function and is activated by phosphorylation of threonine 308 (T308) and serine 473 (S473). While phosphoinositide-dependent kinase 1 (PDK1) is responsible for Akt T308 phosphorylation, the identities of the kinases for Akt S473 phosphorylation in the heart remain controversial. Here, we disrupted mTOR complex 2 (mTORC2) through deletion of Rictor in the heart and found normal heart growth and function. Rictor deletion caused significant reduction of Akt S473 phosphorylation but enhanced Akt T308 phosphorylation, suggesting that a high level of Akt T308 phosphorylation maintains Akt activity and heart function. Deletion of Pdk1 in the heart caused significantly enhanced Akt S473 phosphorylation that was suppressed by removal of Rictor, leading to worsened dilated cardiomyopathy (DCM) and accelerated heart failure in Pdk1-deficient mice. In addition, we found that increasing Akt S473 phosphorylation through deletion of Pten or chemical inhibition of PTEN reversed DCM and heart failure in Pdk1-deficient mice. Investigation of heart samples from human DCM patients revealed changes similar to those in the mouse models. These results demonstrated that PDK1 and mTORC2 synergistically promote postnatal heart growth and maintain heart function in postnatal mice. 相似文献
1000.
W. Mike Henne Lu Zhu Zsolt Balogi Christopher Stefan Jeffrey A. Pleiss Scott D. Emr 《The Journal of cell biology》2015,210(4):541-551
Although endolysosomal trafficking is well defined, how it is regulated and coordinates with cellular metabolism is unclear. To identify genes governing endolysosomal dynamics, we conducted a global fluorescence-based screen to reveal endomembrane effector genes. Screening implicated Phox (PX) domain–containing protein Mdm1 in endomembrane dynamics. Surprisingly, we demonstrate that Mdm1 is a novel interorganelle tethering protein that localizes to endoplasmic reticulum (ER)–vacuole/lysosome membrane contact sites (MCSs). We show that Mdm1 is ER anchored and contacts the vacuole surface in trans via its lipid-binding PX domain. Strikingly, overexpression of Mdm1 induced ER–vacuole hypertethering, underscoring its role as an interorganelle tether. We also show that Mdm1 and its paralogue Ydr179w-a (named Nvj3 in this study) localize to ER–vacuole MCSs independently of established tether Nvj1. Finally, we find that Mdm1 truncations analogous to neurological disease–associated SNX14 alleles fail to tether the ER and vacuole and perturb sphingolipid metabolism. Our work suggests that human Mdm1 homologues may play previously unappreciated roles in interorganelle communication and lipid metabolism. 相似文献