全文获取类型
收费全文 | 2607篇 |
免费 | 227篇 |
国内免费 | 72篇 |
专业分类
2906篇 |
出版年
2023年 | 26篇 |
2022年 | 46篇 |
2021年 | 63篇 |
2020年 | 38篇 |
2019年 | 58篇 |
2018年 | 54篇 |
2017年 | 59篇 |
2016年 | 65篇 |
2015年 | 133篇 |
2014年 | 132篇 |
2013年 | 160篇 |
2012年 | 201篇 |
2011年 | 193篇 |
2010年 | 115篇 |
2009年 | 105篇 |
2008年 | 136篇 |
2007年 | 116篇 |
2006年 | 122篇 |
2005年 | 92篇 |
2004年 | 108篇 |
2003年 | 91篇 |
2002年 | 97篇 |
2001年 | 84篇 |
2000年 | 73篇 |
1999年 | 53篇 |
1998年 | 29篇 |
1997年 | 25篇 |
1996年 | 32篇 |
1995年 | 14篇 |
1994年 | 22篇 |
1993年 | 19篇 |
1992年 | 26篇 |
1991年 | 18篇 |
1990年 | 31篇 |
1989年 | 20篇 |
1988年 | 24篇 |
1987年 | 13篇 |
1986年 | 18篇 |
1985年 | 14篇 |
1984年 | 21篇 |
1983年 | 17篇 |
1981年 | 13篇 |
1979年 | 11篇 |
1978年 | 9篇 |
1977年 | 16篇 |
1976年 | 14篇 |
1975年 | 15篇 |
1974年 | 8篇 |
1972年 | 9篇 |
1969年 | 8篇 |
排序方式: 共有2906条查询结果,搜索用时 15 毫秒
951.
Ho YJ Tai SY Pawlak CR Wang AL Cheng CW Hsieh MH 《The Chinese journal of physiology》2012,55(2):91-100
Neuroimmune system is involved in communication between the endocrine and nervous systems, which may take part in the effects of dioscorea, reversing changes of anxiety-like behavior and interleukin (IL)-2 levels in the brains of ovariectomized (OVX) rats. This study was aimed at evaluating administration of diosgenin, an ingredient of dioscorea, on neuroimmune and behavioral functions in OVX animals. One month after ovariectomy, female Wistar rats were fed daily with diosgenin (0, 10, 50 or 100 mg/kg/day) and the elevated plus-maze and learned helplessness tests were used to measure anxiety-like and depressive behaviors after 23 and 24 days of diosgenin treatment, respectively. In the learned helplessness test, the rats needed to cross from one compartment of the shuttle box to the opposite compartment to avoid or escape the shock. If the rat failed to escape the shock in 10 sec, a "failure" was recorded. Two days after the behavioral tests, the brain was removed to measure levels of IL-2 which was used as an indicator of neuroimmune function. Anxiety-like behavior in the OVX rats was not affected by diosgenin treatment. However, avoidance behavior in the learned helplessness test in the OVX rats with high anxiety (HA) levels was improved by treatment with diosgenin at the dosage of 10mg/kg/day. Interestingly, the number of failures in the same test was increased when the dosage of diosgenin was increased to 50 mg/kg/day, and this was accompanied by an increase in IL-2 levels in the pituitary gland. In addition, treatment with 100 mg/kg/day of diosgenin resulted in decreased IL-2 levels in the amygdala and prefrontal cortex of the OVX rats with low anxiety levels, and in increased IL-2 levels in the amygdala of OVX HA rats. These results show that chronic diosgenin treatment influences IL-2 levels in the brain of OVX rats and affects depressive behavior in OVX HA rats, but not OVX low anxiety rats. 相似文献
952.
ML Kung HE Tsai TH Hu HM Kuo LF Liu SC Chen PR Lin YL Ma EM Wang GS Liu JK Liu MH Tai 《Biochemical and biophysical research communications》2012,425(2):169-176
Hepatoma-derived growth factor (HDGF) stimulates the migration, invasion and metastasis in several types of cancer cells. However, the mechanism underlying HDGF-stimulated migration remains unclear. In this study, we investigated the influence of HDGF on cytoskeleton remodeling and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in non-transformed NIH/3T3 cells. Exogenous HDGF promoted the migration and the formation of dorsal ruffles and podosome rosettes. Besides, HDGF supply increased the PI3K expression and Akt phosphorylation in dose- and time-dependent manners. Application of LY294002, a PI3K inhibitor, attenuated the HDGF-induced migration, dorsal ruffles and podosome rosettes formation. Consistently, the HDGF-overexpressing NIH/3T3 transfectants exhibited significantly increased motility and elevated PI3K/Akt activities, which were repressed by LY294002 or adenovirus-mediated overexpression of endogenous PI3K antagonist, PTEN. In summary, HDGF elicits the activation of PI3K/Akt signaling cascade, thereby promoting cytoskeleton remodeling to stimulate cellular migration. 相似文献
953.
LaDu MJ Munson GW Jungbauer L Getz GS Reardon CA Tai LM Yu C 《Biochimica et biophysica acta》2012,1821(2):295-302
The association between apolipoprotein E (apoE) and amyloid-β peptide (Aβ) may significantly impact the function of both proteins, thus affecting the etiology of Alzheimer's disease (AD). However, apoE/Aβ interactions remain fundamentally defined by the stringency of the detection method. Here we use size exclusion chromatography (SEC) as a non-stringent approach to the detection of apoE/Aβ interactions in solution, specifically apoE and both endogenous and exogenous Aβ from plasma, CSF and astrocyte conditioned media. By SEC analysis, Aβ association with plasma and CNS lipoproteins is apoE-dependent. While endogenous Aβ elutes to specific human plasma lipoproteins distinct from those containing apoE, it is the apoE-containing lipoproteins that absorb excess amounts of exogenous Aβ40. In human CSF, apoE, endogenous Aβ and phospholipid elute in an almost identical profile, as do apoE, exogenous Aβ and phospholipid from astrocyte conditioned media. Combining SEC fractionation with subsequent analysis for SDS-stable apoE/Aβ complex reveals that apoE-containing astrocyte lipoproteins exhibit the most robust interactions with Aβ. Thus, standardization of the methods for detecting apoE/Aβ complex is necessary to determine its functional significance in the neuropathology characteristic of AD. Importantly, a systematic understanding of the role of apoE-containing plasma and CNS lipoproteins in Aβ homeostasis could potentially contribute to identifying a plasma biomarker currently over-looked because it has multiple components. 相似文献
954.
Kwon J Han E Bui CB Shin W Lee J Lee S Choi YB Lee AH Lee KH Park C Obin MS Park SK Seo YJ Oh GT Lee HW Shin J 《EMBO reports》2012,13(2):150-156
Sqstm1/p62 functions in the non-canonical activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, its physiological relevance is not certain. Here, we show that p62(-/-) mice exhibited an accelerated presentation of ageing phenotypes, and tissues from these mice created a pro-oxidative environment owing to compromised mitochondrial electron transport. Accordingly, mitochondrial function rapidly declined with age in p62(-/-) mice. In addition, p62 enhanced basal Nrf2 activity, conferring a higher steady-state expression of NAD(P)H dehydrogenase, quinone 1 (Nqo1) to maintain mitochondrial membrane potential and, thereby, restrict excess oxidant generation. Together, the p62-Nrf2-Nqo1 cascade functions to assure mammalian longevity by stabilizing mitochondrial integrity. 相似文献
955.
956.
957.
Lys89, Lys90, and Phe91 are critical core amino acid residues of the Pen ch 18 major fungal allergen recognized by human IgE antibodies 总被引:1,自引:0,他引:1
Cheng TT Tam MF Chou H Tai HY Shen HD 《Biochemical and biophysical research communications》2008,375(4):671-674
A vacuolar serine protease (Pen ch 18) has been identified as a major allergen of Penicillium chrysogenum. The molecular features of antigenic determinant(s) on Pen ch 18 recognized by human IgE antibodies, however, have remained unclear. Here, we show that a dominant IgE epitope on the N-terminally processed Pen ch 18 allergen was narrowed down to residues 83-91. In addition, Lys89, Lys90, and possibly Phe91 were identified as the core residues. Substitution of Lys89, Lys90, or Phe91 with alanine can significantly reduce IgE-binding to Pen ch 18. Immunoblot inhibition confirmed that Lys89 and Phe91 played a significant role in IgE-binding against Pen ch 18. Molecular modeling suggests they are located on a loop-like structure at or near the surface of the major fungal allergen. 相似文献
958.
O-Acetylserine sulfhydrylase catalyzes the final step of the biosynthesis of L-cysteine, the replacement of the beta-acetoxy group of O-acetyl-L-serine (OAS) by a thiol. The enzyme undergoes a conformational change to close the site upon formation of the external Schiff base (ESB) with OAS. Mutation of K120 to Q was predicted to destabilize the closed form of the ESB and decrease the rate. The K120Q mutant enzyme was prepared and characterized by UV-visible absorbance, fluorescence, visible CD, and 31P NMR spectral studies, as well as steady state and pre-steady state kinetic studies. Spectra suggest a shift in the tautomeric equilibrium toward the neutral enolimine and an increase in the rate of interconversion of the open and closed forms of the enzyme. A decrease in the rate of both half reactions likely reflects the stabilization of the ESB as a result of the increased rate of equilibration of the open and closed forms of the enzyme along the reaction pathway. Data suggest a role of K120 in helping to stabilize the closed conformation by participating in a new hydrogen bond to the backbone carbonyl of A231. 相似文献
959.
SecA is an essential component in the Sec-dependent protein translocation pathway and, together with ATP, provides the driving force for the transport of secretory proteins across the cytoplasmic membrane of Escherichia coli. Previous studies established that SecA undergoes monomer-dimer equilibrium in solution. However, the oligomeric state of functional SecA during the protein translocation process is controversial. In this study, we provide additional evidence that SecA functions as a dimer in the membrane by (i) demonstration of the capability of the presumably monomeric SecA derivative to be cross-linked as dimers in vitro and in vivo, (ii) complementation of the growth of a secA(Ts) mutant with another nonfunctional SecA or (iii) in vivo complementation and in vitro function of a genetically tandem SecA dimer that does not dissociate into monomers, and (iv) formation of similar ring-like structures by the tandem SecA dimer and SecA in the presence of lipid bilayers. We conclude that SecA functions as a dimer in the membrane and dissociation into monomers is not necessary during protein translocation. 相似文献
960.
Occurrence, seasonality and genetic diversity of Vibrio vulnificus in coastal seaweeds and water along the Kii Channel, Japan 总被引:1,自引:0,他引:1
Mahmud ZH Neogi SB Kassu A Mai Huong BT Jahid IK Islam MS Ota F 《FEMS microbiology ecology》2008,64(2):209-218
Vibrio vulnificus is a ubiquitous toxigenic bacterium found in a coastal environment but little is known about its occurrence and seasonality among seaweeds, which are widely consumed as seafood in Japan. Therefore, we have observed the bacterium's abundance in seawater and seaweed samples from three areas of the Kii Channel, Japan, during June 2003 to May 2004. A total of 192 samples were collected: 24 from each source in summer, autumn, winter and spring. The samples were selectively cultivated following the most probable number (MPN) technique. Vibrio vulnificus population ranged from 0 to 10(3) MPN 100 mL(-1) seawater or 10 g seaweeds; higher counts were observed during summer. The optimum temperature, salinity and pH for the bacterium were 20-24 degrees C, 24-28 p.p.t. and 7.95-8.15, respectively. However, seaweeds always contained higher V. vulnificus than seawater. Among 280 V. vulnificus strains, detected by species-specific colony hybridization and PCR, 78, 74, 11 and 16 were from seaweeds and 46, 42, 2 and 11 were from seawater during summer, autumn, winter and spring, respectively. Ribotyping of 160 selected strains revealed a higher genotypic diversity (18 patterns) among strains from seaweeds than from seawater (10 patterns). Seaweeds can thus act as a potential habitat for V. vulnificus and are more unsafe for consumption during summer. 相似文献