全文获取类型
收费全文 | 44068篇 |
免费 | 4035篇 |
国内免费 | 6159篇 |
专业分类
54262篇 |
出版年
2024年 | 146篇 |
2023年 | 599篇 |
2022年 | 1389篇 |
2021年 | 2216篇 |
2020年 | 1636篇 |
2019年 | 2047篇 |
2018年 | 1911篇 |
2017年 | 1500篇 |
2016年 | 2023篇 |
2015年 | 2958篇 |
2014年 | 3555篇 |
2013年 | 3664篇 |
2012年 | 4416篇 |
2011年 | 4096篇 |
2010年 | 2598篇 |
2009年 | 2286篇 |
2008年 | 2654篇 |
2007年 | 2388篇 |
2006年 | 2095篇 |
2005年 | 1754篇 |
2004年 | 1483篇 |
2003年 | 1327篇 |
2002年 | 1156篇 |
2001年 | 717篇 |
2000年 | 604篇 |
1999年 | 540篇 |
1998年 | 363篇 |
1997年 | 318篇 |
1996年 | 273篇 |
1995年 | 220篇 |
1994年 | 210篇 |
1993年 | 141篇 |
1992年 | 156篇 |
1991年 | 126篇 |
1990年 | 95篇 |
1989年 | 93篇 |
1988年 | 77篇 |
1987年 | 50篇 |
1986年 | 58篇 |
1985年 | 65篇 |
1984年 | 27篇 |
1983年 | 37篇 |
1982年 | 32篇 |
1981年 | 28篇 |
1980年 | 12篇 |
1979年 | 25篇 |
1978年 | 14篇 |
1974年 | 9篇 |
1973年 | 11篇 |
1971年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 11 毫秒
91.
Wei Gu Feng Pan Honglai Zhang Gary J Bassell Robert H Singer 《The Journal of cell biology》2002,156(1):41-51
The localization of beta-actin mRNA to the leading lamellae of chicken fibroblasts and neurite growth cones of developing neurons requires a 54-nt localization signal (the zipcode) within the 3' untranslated region. In this study we have identified and isolated five proteins binding to the zipcode. One of these we previously identified as zipcode binding protein (ZBP)1, a 4-KH domain protein. A second is now investigated in detail: a 92-kD protein, ZBP2, that is especially abundant in extracts from embryonic brain. We show that ZBP2 is a homologue of the human hnRNP protein, KSRP, that appears to mediate pre-mRNA splicing. However, ZBP2 has a 47-amino acid (aa) sequence not present in KSRP. Various portions of ZBP2 fused to GFP indicate that the protein most likely shuttles between the nucleus and the cytoplasm, and that the 47-aa insert promotes the nuclear localization. Expression of a truncated ZBP2 inhibits the localization of beta-actin mRNA in both fibroblast and neurons. These data suggest that ZBP2, although predominantly a nuclear protein, has a role in the cytoplasmic localization of beta-actin mRNA. 相似文献
92.
Meshail Okla Wei Wang Inhae Kang Anjeza Pashaj Timothy Carr Soonkyu Chung 《The Journal of biological chemistry》2015,290(44):26476-26490
Adaptive thermogenesis is the cellular process transforming chemical energy into heat in response to cold. A decrease in adaptive thermogenesis is a contributing factor to obesity. However, the molecular mechanisms responsible for the compromised adaptive thermogenesis in obese subjects have not yet been elucidated. In this study we hypothesized that Toll-like receptor 4 (TLR4) activation and subsequent inflammatory responses are key regulators to suppress adaptive thermogenesis. To test this hypothesis, C57BL/6 mice were either fed a palmitate-enriched high fat diet or administered with chronic low-dose LPS before cold acclimation. TLR4 stimulation by a high fat diet or LPS were both associated with reduced core body temperature and heat release. Impairment of thermogenic activation was correlated with diminished expression of brown-specific markers and mitochondrial dysfunction in subcutaneous white adipose tissue (sWAT). Defective sWAT browning was concomitant with elevated levels of endoplasmic reticulum (ER) stress and autophagy. Consistently, TLR4 activation by LPS abolished cAMP-induced up-regulation of uncoupling protein 1 (UCP1) in primary human adipocytes, which was reversed by silencing of C/EBP homologous protein (CHOP). Moreover, the inactivation of ER stress by genetic deletion of CHOP or chemical chaperone conferred a resistance to the LPS-induced suppression of adaptive thermogenesis. Collectively, our data indicate the existence of a novel signaling network that links TLR4 activation, ER stress, and mitochondrial dysfunction, thereby antagonizing thermogenic activation of sWAT. Our results also suggest that TLR4/ER stress axis activation may be a responsible mechanism for obesity-mediated defective brown adipose tissue activation. 相似文献
93.
The RhoA/ROCK-2 signaling pathway is necessary for activated hepatic stellate cell (HSC) contraction. HSC contraction plays an important role in the pathogenesis of cirrhosis and portal hypertension. This study investigated whether aldosterone contributes to HSC contraction by activation of the RhoA/ROCK-2 signaling pathway. Primary HSCs were isolated from Sprague-Dawley rats via in situ pronase/collagenase perfusion. We found that aldosterone enhanced the contraction of a collagen lattice seeded with HSCs. This induced contraction was suppressed by the mineralcorticoid receptor (MR) inhibitor spironolactone, the ROCK-2 inhibitor Y27632, and the angiotensin II type 1 receptor (AT(1)R) inhibitor irbesartan. Moreover, actin fiber staining showed that aldosterone significantly increased actin fiber formation in HSCs. Pre-incubating with spironolactone, Y27632, or irbesartan inhibited the aldosterone-induced actin fiber reorganization. Molecularly, the effect of aldosterone on activation of HSC contraction was mediated by phosphorylated myosin light chain (P-MLC) through the RhoA/ROCK-2 signaling pathway. All these inhibitors had the ability to block aldosterone-induced protein expressions in the RhoA/ROCK-2/P-MLC cascade in HSCs. Taken together, our current study suggests that aldosterone induces contraction of activated HSCs through the activation of the RhoA/ROCK-2 signaling pathway. This finding may provide a potential therapeutic target for control of cirrhosis and portal hypertension. 相似文献
94.
Rahmani M Susidarti RA Ismail HB Sukari MA Hin TY Lian GE Ali AM Kulip J Waterman PG 《Phytochemistry》2003,64(4):873-877
In a continuation of our study of the Rutaceae, detailed chemical investigation on Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia gave four new coumarins. The structures of the coumarins have been fully characterised by spectroscopic methods as 3",4"-dihydrocapnolactone 1, 2',3'-epoxyisocapnolactone 2, 8-hydroxyisocapnolactone-2',3'-diol 3 and 8-hydroxy-3",4"-dihydrocapnolactone-2',3'-diol 4. 相似文献
95.
HongYuan Wei YuXuan Ye HaiJian Huang MingShun Chen ZiXiang Yang XiaoMing Chen ChuanXi Zhang 《Ecology and evolution》2022,12(4)
The aphid Schlechtendalia chinensis is an economically important insect that can induce horned galls, which are valuable for the medicinal and chemical industries. Up to now, more than twenty aphid genomes have been reported. Most of the sequenced genomes are derived from free‐living aphids. Here, we generated a high‐quality genome assembly from a galling aphid. The final genome assembly is 271.52 Mb, representing one of the smallest sequenced genomes of aphids. The genome assembly is based on contig and scaffold N50 values of the genome sequence are 3.77 Mb and 20.41 Mb, respectively. Nine‐seven percent of the assembled sequences was anchored onto 13 chromosomes. Based on BUSCO analysis, the assembly involved 96.9% of conserved arthropod and 98.5% of the conserved Hemiptera single‐copy orthologous genes. A total of 14,089 protein‐coding genes were predicted. Phylogenetic analysis revealed that S. chinensis diverged from the common ancestor of Eriosoma lanigerum approximately 57 million years ago (MYA). In addition, 35 genes encoding salivary gland proteins showed differentially when S. chinensis forms a gall, suggesting they have potential roles in gall formation and plant defense suppression. Taken together, this high‐quality S. chinensis genome assembly and annotation provide a solid genetic foundation for future research to reveal the mechanism of gall formation and to explore the interaction between aphids and their host plants. 相似文献
96.
97.
Diversity of endophytic bacteria within nodules of the Sphaerophysa salsula in different regions of Loess Plateau in China 总被引:1,自引:0,他引:1
Deng ZS Zhao LF Kong ZY Yang WQ Lindström K Wang ET Wei GH 《FEMS microbiology ecology》2011,76(3):463-475
A total of 115 endophytic bacteria were isolated from root nodules of the wild legume Sphaerophysa salsula grown in two ecological regions of Loess Plateau in China. The genetic diversity and phylogeny of the strains were revealed by restriction fragment length polymorphism and sequencing of 16S rRNA gene and enterobacterial repetitive intergenic consensus-PCR. Their symbiotic capacity was checked by nodulation tests and analysis of nifH gene sequence. This is the first systematic study on endophytic bacteria associated with S. salsula root nodules. Fifty of the strains found were symbiotic bacteria belonging to eight putative species in the genera Mesorhizobium, Rhizobium and Sinorhizobium, harboring similar nifH genes; Mesorhizobium gobiense was the main group and 65 strains were nonsymbiotic bacteria related to 17 species in the genera Paracoccus, Sphingomonas, Inquilinus, Pseudomonas, Serratia, Mycobacterium, Nocardia, Streptomyces, Paenibacillus, Brevibacillus, Staphylococcus, Lysinibacillus and Bacillus, which were universally coexistent with symbiotic bacteria in the nodules. Differing from other similar studies, the present study is the first time that symbiotic and nonsymbiotic bacteria have been simultaneously isolated from the same root nodules, offering the possibility to accurately reveal the correlation between these two kinds of bacteria. These results provide valuable information about the interactions among the symbiotic bacteria, nonsymbiotic bacteria and their habitats. 相似文献
98.
The electrostatic force including the intramolecular Coulombic interactions and the electrostatic contribution of solvation effect were entirely calculated by using the finite difference Poisson-Boltzmann method (FDPB), which was incorporated into the GROMOS96 force field to complete a new finite difference stochastic dynamics procedure (FDSD). Simulations were performed on an insulin dimer. Different relative dielectric constants were successively assigned to the protein interior; a value of 17 was selected as optimal for our system. The simulation data were analyzed and compared with those obtained from 500-ps molecular dynamics (MD) simulation with explicit water and a 500-ps conventional stochastic dynamics (SD) simulation without the mean solvent force. The results indicate that the FDSD method with GROMOS96 force field is suitable to study the dynamics and structure of proteins in solution if used with the optimal protein dielectric constant. 相似文献
99.
紫翅猪毛菜的种子多型性及其结实格局 总被引:7,自引:0,他引:7
紫翅猪毛菜(Salsola affinis)主要分布于新疆准噶尔荒漠, 具有很强的抗干旱和耐盐碱能力, 其种子具有多型现象。我们对紫翅猪毛菜的种子形态、萌发特性及结实格局进行了观测研究。结果表明: (1) 紫翅猪毛菜3种类型的种子在形状、大小、颜色、着生方式及包被其花被片背部是否具翅方面均有明显不同; (2) 3种类型的种子具有不同的散布特性和萌发行为: A型种子容易从母体脱落, 发达的果翅能够借助风进行远距离传播; B、C型种子成熟时紧连母体, 不易脱落。在变温下A型种子和B型种子能够快速萌发, 且B型种子比A型种子的萌发速度快; 而C型种子萌发缓慢, 最终萌发率小于10%, 表明其处于休眠状态; (3)随植株个体的增大, A型种子所占比例逐渐增多, 由0.43%增加到51.07%; B型种子所占比例逐渐减少, 由65.80%减少到18.06%; C型种子所占比例没有显著变化, 约为30–35%。紫翅猪毛菜的种子多型性以及种子输出的灵活性有利于其在荒漠异质环境中成功定居。对种子多型性及其结实格局的研究将为探讨其生态适应机制及生活史进化研究提供科学依据。 相似文献
100.
Zheng P Gao HC Li Q Shao WH Zhang ML Cheng K Yang de Y Fan SH Chen L Fang L Xie P 《Journal of proteome research》2012,11(3):1741-1748
Major depressive disorder (MDD) is a socially detrimental psychiatric disorder, contributing to increased healthcare expenditures and suicide rates. However, no empirical laboratory-based tests are available to support the diagnosis of MDD. In this study, a NMR-based plasma metabonomic method for the diagnosis of MDD was tested. Proton nuclear magnetic resonance ((1)H NMR) spectra of plasma sampled from first-episode drug-na??ve depressed patients (n = 58) and healthy controls (n = 42) were recorded and analyzed by orthogonal partial least-squares discriminant analysis (OPLS-DA). The OPLS-DA score plots of the spectra demonstrated that the depressed patient group was significantly distinguishable from the healthy control group. Moreover, the method accurately diagnosed blinded samples (n = 26) in an independent replication cohort with a sensitivity and specificity of 92.8% and 83.3%, respectively. Taken together, NMR-based plasma metabonomics may offer an accurate empirical laboratory-based method applicable to the diagnosis of MDD. 相似文献