首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1838篇
  免费   122篇
  国内免费   2篇
  1962篇
  2022年   14篇
  2021年   22篇
  2020年   7篇
  2019年   13篇
  2018年   24篇
  2017年   29篇
  2016年   43篇
  2015年   68篇
  2014年   72篇
  2013年   108篇
  2012年   125篇
  2011年   123篇
  2010年   67篇
  2009年   66篇
  2008年   125篇
  2007年   117篇
  2006年   107篇
  2005年   102篇
  2004年   100篇
  2003年   98篇
  2002年   101篇
  2001年   39篇
  2000年   34篇
  1999年   32篇
  1998年   20篇
  1997年   15篇
  1996年   11篇
  1995年   18篇
  1994年   27篇
  1993年   14篇
  1992年   28篇
  1991年   12篇
  1990年   20篇
  1989年   21篇
  1988年   23篇
  1987年   13篇
  1986年   24篇
  1985年   16篇
  1984年   9篇
  1983年   9篇
  1982年   15篇
  1981年   5篇
  1980年   4篇
  1979年   3篇
  1978年   3篇
  1977年   3篇
  1974年   2篇
  1973年   2篇
  1972年   4篇
  1966年   1篇
排序方式: 共有1962条查询结果,搜索用时 15 毫秒
81.
82.
Applied Entomology and Zoology - Juvenile hormone (JH) has crucial roles in insect physiology, including development, reproduction, and polyphenism. JH is synthesized in the corpora allata (CA)...  相似文献   
83.
Legionella pneumophila (L. pneumophila) is a gram-negative bacterium that replicates in a compartment that resembles the host endoplasmic reticulum (ER). To create its replicative niche, L. pneumophila manipulates host membrane traffic and fusion machineries. Bacterial proteins called Legionella effectors are translocated into the host cytosol and play a crucial role in these processes. In an early stage of infection, Legionella subverts ER-derived vesicles (ERDVs) by manipulating GTPase Rab1 to facilitate remodeling of the Legionella-containing vacuole (LCV). Subsequently, the LCV associates with the ER in a mechanism that remains elusive. In this study, we show that L. pneumophila recruits GTPases Rab33B and Rab6A, which regulate vesicle trafficking from the Golgi to the ER, to the LCV to promote the association of LCV with the ER. We found that recruitment of Rab6A to the LCV depends on Rab33B. Legionella effector SidE family proteins, which phosphoribosyl-ubiquitinate Rab33B, were found to be necessary for the recruitment of Rab33B to the LCV. Immunoprecipitation experiments revealed that L. pneumophila facilitates the interaction of Rab6 with ER-resident SNAREs comprising syntaxin 18, p31, and BNIP1, but not tethering factors including NAG, RINT-1, and ZW10, which are normally required for syntaxin 18-mediated fusion of Golgi-derived vesicles with the ER. Our results identified a Rab33B-Rab6A cascade on the LCV and the interaction of Rab6 with ER-resident SNARE proteins for the association of LCV with the ER and disclosed the unidentified physiological role of SidE family proteins.  相似文献   
84.
Fungicide activity through activation of a fungal signalling pathway   总被引:3,自引:0,他引:3  
Fungicides generally inhibit enzymatic reactions involved in fungal cellular biosynthesis. Here we report, for the first time, an example of fungicidal effects through hyperactivation of a fungal signal transduction pathway. The OSC1 gene, encoding a MAP kinase (MAPK) related to yeast Hog1, was isolated from the fungal pathogen Colletotrichum lagenarium that causes cucumber anthracnose. The osc1 knockout mutants were sensitive to high osmotic stress and showed increased resistance to the fungicide fludioxonil, indicating that Osc1 is involved in responses to hyperosmotic stress and sensitivity to fludioxonil. The Osc1 MAPK is phosphorylated under high osmotic conditions, indicating activation of Osc1 by high osmotic stress. Importantly, fludioxonil treatment also activates phosphorylation of Osc1, suggesting that improper activation of Osc1 by fludioxonil has negative effects on fungal growth. In the presence of fludioxonil, the wild-type fungus was not able to infect the host plant because of a failure of appressorium-mediated penetration, whereas osc1 mutants successfully infected plants. Analysis using a OSC1-GFP fusion gene indicated that Osc1 is rapidly translocated to the nucleus in appressorial cells after the addition of fludioxonil, suggesting that fludioxonil impairs the function of infection structures by activation of Osc1. Furthermore, fludioxonil activates Hog1-type MAPKs in the plant pathogenic fungi Cochliobolus heterostrophus and Botrytis cinerea. These results strongly suggest that fludioxonil acts as a fungicide, in part, through activation of the MAPK cascade in fungal pathogens.  相似文献   
85.
Nest-building is a great ape universal and arboreal nesting in chimpanzees and bonobos suggests that the common ancestor of Pan and Homo also nested in trees. It has been proposed that arboreal nest-building remained the prevailing pattern until Homo erectus, a fully terrestrial biped, emerged. We investigated the unusual occurrence of ground-nesting in chimpanzees (Pan troglodytes), which may inform on factors influencing the tree-to-ground sleep transition in the hominin lineage. We used a novel genetic approach to examine ground-nesting in unhabituated chimpanzees at Seringbara in the Nimba Mountains, Guinea. Previous research showed that ground-nesting at Seringbara was not ecologically determined. Here, we tested a possible mate-guarding function of ground-nesting by analyzing DNA from shed hairs collected from ground nests and tree nests found in close proximity. We examined whether or not ground-nesting was a group-level behavioral pattern and whether or not it occurred in more than one community. We used multiple genetic markers to identify sex and to examine variation in mitochondrial DNA control region (HV1, HV2) sequences. Ground-nesting was a male-biased behavior and males constructed more elaborate ("night") nests than simple ("day") nests on the ground. The mate-guarding hypothesis was not supported, as ground and associated tree nests were built either by maternally-related males or possibly by the same individuals. Ground-nesting was widespread and likely habitual in two communities. We suggest that terrestrial nest-building may have already occurred in arboreally-adapted early hominins before the emergence of H. erectus.  相似文献   
86.
87.
Hepatitis C virus (HCV) core protein plays an important role in the formation of the viral nucleocapsid and a regulatory protein involved in hepatocarcinogenesis. In this study, we have identified proteasome activator PA28gamma (11S regulator gamma) as an HCV core binding protein by using yeast two-hybrid system. This interaction was demonstrated not only in cell culture but also in the livers of HCV core transgenic mice. These findings are extended to human HCV infection by the observation of this interaction in liver specimens from a patient with chronic HCV infection. Neither the interaction of HCV core protein with other PA28 subtypes nor that of PA28gamma with other Flavivirus core proteins was detected. Deletion of the PA28gamma-binding region from the HCV core protein or knockout of the PA28gamma gene led to the export of the HCV core protein from the nucleus to the cytoplasm. Overexpression of PA28gamma enhanced the proteolysis of the HCV core protein. Thus, the nuclear retention and stability of the HCV core protein is regulated via a PA28gamma-dependent pathway through which HCV pathogenesis may be exerted.  相似文献   
88.
To assess the relationship between blood volume (BV) and the reduction in plasma volume (PV) during exercise in individual variations, we measured BV and changes in PV in thirteen male volunteers during treadmill exercise until exhaustion. The lactate threshold (LT), as a predictor of aerobic exercise capacity, was calculated from the exercise intensity at the point of plasma lactate concentration buildup to 4 mmol. The relationship of peak VO2 with BV indicated a significant positive correlation. The strong positive relation between the shifts in PV and total PV, and resulted in a maintenance of the circulating BV.  相似文献   
89.
Cytotoxic T-lymphocyte (CTL) responses are crucial for the control of immunodeficiency virus replication. Possible involvement of a dominant single epitope-specific CTL in control of viral replication has recently been indicated in preclinical AIDS vaccine trials, but it has remained unclear if multiple epitope-specific CTLs can be involved in the vaccine-based control. Here, by following up five rhesus macaques that showed vaccine-based control of primary replication of a simian immunodeficiency virus, SIVmac239, we present evidence indicating involvement of multiple epitope-specific CTL responses in this control. Three macaques maintained control for more than 2 years without additional mutations in the provirus. However, in the other two that shared a major histocompatibility complex haplotype, viral mutations were accumulated in a similar order, leading to viral evasion from three epitope-specific CTL responses with viral fitness costs. Accumulation of these multiple escape mutations resulted in the reappearance of plasma viremia around week 60 after challenge. Our results implicate multiple epitope-specific CTL responses in control of immunodeficiency virus replication and furthermore suggest that sequential accumulation of multiple CTL escape mutations, if allowed, can result in viral evasion from this control.  相似文献   
90.
Hypertrophy of adipocytes in obese adipose tissues causes metabolic abnormality by adipocytokine dysregulation, which promotes type 2 diabetes mellitus, hypertension, and dyslipidemia. We investigated the effects of wasabi (Wasabia japonica Matsum) leaf extracts on metabolic abnormalities in SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP/ZF), which are a model of metabolic syndrome. Male SHRSP/ZF rats aged 7 weeks were divided into two groups: control and wasabi leaf extract (WLE) groups, which received water or oral treatment with 4 g/kg/day WLE for 6 weeks. WLE improved the body weight gain and high blood pressure in SHRSP/ZF rats, and the plasma triglyceride levels were significantly lower in the WLE group. Adipocyte hypertrophy was markedly prevented in adipose tissue. The expression of PPARγ and subsequent downstream genes was suppressed in the WLE group adipose tissues. Our data suggest that WLE inhibits adipose hypertrophy by suppressing PPARγ expression in adipose tissue and stimulating the AMPK activity by increased adiponectin.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号