全文获取类型
收费全文 | 1245篇 |
免费 | 155篇 |
国内免费 | 509篇 |
出版年
2024年 | 18篇 |
2023年 | 25篇 |
2022年 | 30篇 |
2021年 | 36篇 |
2020年 | 24篇 |
2019年 | 36篇 |
2018年 | 29篇 |
2017年 | 15篇 |
2016年 | 30篇 |
2015年 | 39篇 |
2014年 | 57篇 |
2013年 | 41篇 |
2012年 | 122篇 |
2011年 | 115篇 |
2010年 | 52篇 |
2009年 | 71篇 |
2008年 | 106篇 |
2007年 | 82篇 |
2006年 | 78篇 |
2005年 | 92篇 |
2004年 | 97篇 |
2003年 | 104篇 |
2002年 | 49篇 |
2001年 | 75篇 |
2000年 | 53篇 |
1999年 | 57篇 |
1998年 | 29篇 |
1997年 | 20篇 |
1996年 | 24篇 |
1995年 | 21篇 |
1994年 | 35篇 |
1993年 | 26篇 |
1992年 | 20篇 |
1991年 | 25篇 |
1990年 | 14篇 |
1989年 | 18篇 |
1988年 | 8篇 |
1987年 | 20篇 |
1986年 | 12篇 |
1985年 | 4篇 |
1984年 | 13篇 |
1983年 | 15篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1964年 | 10篇 |
1963年 | 6篇 |
1962年 | 4篇 |
1958年 | 3篇 |
排序方式: 共有1909条查询结果,搜索用时 46 毫秒
131.
132.
研究了枯水期淮河淮南段及巢湖西半湖水质污染对鲫鱼的毒性效应。从淮河淮南段与巢湖采集鱼类样本,并以未受人为污染的安丰塘鱼类为对照,分析了鲫鱼肝脏丙二醛(Malondialdehyde,MDA)含量、超氧化物歧化酶(Superoxide dismutase,SOD)活性、谷胱甘肽硫转移酶(Glutathione S-transferase,GST)活性、7-乙氧基异吩恶唑-O-脱乙基酶(7-ethoxyresorufin-O-deethylase,EROD)活性及DNA单链损伤情况,结果表明,淮河淮南段鲫鱼肝脏MDA含量、SOD活性、GST活性、EROD活性均高于对照组,分别是对照组的2.88、1.48、2.03和3.93倍;巢湖鲫鱼肝脏MDA含量、SOD活性、EROD活性均高于对照组,分别是对照组的2.28、1.85和2.74倍。肝细胞DNA单链断裂的测定显示淮河淮南段与巢湖的水质污染均对鲫鱼有遗传毒性。 相似文献
133.
134.
135.
Loss of PTEN is the earliest detectable genetic lesion in the endometrioid subtype of endometrial cancer (EEC), a tumor thought to be associated with an increase in unopposed estrogen activity. Pten(+/-) mice develop endometrial neoplastic lesions with full penetrance, despite having normal estrogen levels. We have utilized oligonucleotide arrays to identify the alterations in gene expression patterns associated with loss of Pten and consequent neoplastic transformation of the endometrium. We show that 487 and 330 genes are substantially up- and downregulated, respectively, in Pten(+/-) mice. Several genes whose expression levels are impacted by loss of Pten are associated with pathways and functions that are relevant to the transformation and progression processes. Strikingly, we found that the expression levels of over 100 genes known to be regulated by estrogen receptor alpha (ERalpha) are also altered in the neoplastic uterus from Pten(+/-) mice, thus mimicking a hyperestrogenic environment. These results provide in vivo evidence supporting the hypothesis that loss of Pten and subsequent Akt activation result in the activation of several ERalpha-dependent pathways that, mimicking increased estrogen signaling, may play a pivotal role in the neoplastic process. 相似文献
136.
ExoS of Pseudomonas aeruginosa induces apoptosis through a Fas receptor/caspase 8-independent pathway in HeLa cells 总被引:1,自引:0,他引:1
Pseudomonas aeruginosa infection is a serious complication in immunocompromised individuals and in patients with cystic fibrosis. We have previously shown that the type III secreted effector ExoS triggers apoptosis in various cultured cell lines via its ADP-ribosyltransferase (ADPRT) activity. The apoptosis process was further shown to involve intrinsic signalling pathway requiring c-Jun N-terminal kinase (JNK)-initiated mitochondrial pathway. In the present study, we investigated the role of Fas pathway activation in P. aeruginosa-induced apoptosis. P. aeruginosa infection resulted in caspase 8 cleavage in HeLa cells, which was inhibited by overexpression of a dominant negative version of Fas-associated death domain (FADD), suggesting that Fas pathway was activated. In fact, confocal laser scanning microscopy showed that P. aeruginosa induced clustering of FasR. In addition, the ADPRT activity of the ExoS was required for the induction of FasR clustering and caspase 8 cleavage. However, blocking the FasR-FasL interaction by antagonistic antibodies to FasR or to FasL had no effect on P. aeruginosa-induced caspase 8 and caspase 3 activation, neither did the silencing of FasR by small interfering RNA (siRNA), suggesting that caspase 8 activation through the FADD bypasses FasR/FasL-mediated signalling. Thus, FADD-mediated caspase 8 activation involves intracellular ExoS in an ADPRT-dependent manner. Furthermore, silencing of caspase 8 by siRNA did not interfere with P. aeruginosa-induced apoptosis, whereas it rendered HeLa cells markedly increased resistance towards FasL-induced apoptosis. In conclusion, our findings indicate that ExoS of P. aeruginosa induces apoptosis through a mechanism that is independent of Fas receptor/caspase 8 pathway. 相似文献
137.
Phelan MM Goult BT Clayton JC Hautbergue GM Wilson SA Lian LY 《Nucleic acids research》2012,40(7):3232-3244
SRSF2 is a prototypical SR protein which plays important roles in the alternative splicing of pre-mRNA. It has been shown to be involved in regulatory pathways for maintaining genomic stability and play important roles in regulating key receptors in the heart. We report here the solution structure of the RNA recognition motifs (RRM) domain of free human SRSF2 (residues 9-101). Compared with other members of the SR protein family, SRSF2 structure has a longer L3 loop region. The conserved aromatic residue in the RNP2 motif is absent in SRSF2. Calorimetric titration shows that the RNA sequence 5'AGCAGAGUA3' binds SRSF2 with a K(d) of 61 ± 1 nM and a 1:1 stoichiometry. NMR and mutagenesis experiments reveal that for SFSF2, the canonical β1 and β3 interactions are themselves not sufficient for effective RNA binding; the additional loop L3 is crucial for RNA complex formation. A comparison is made between the structures of SRSF2-RNA complex with other known RNA complexes of SR proteins. We conclude that interactions involving the L3 loop, N- and C-termini of the RRM domain are collectively important for determining selectivity between the protein and RNA. 相似文献
138.
Wan Y Wu YL Lian LH Xie WX Li X Ouyang BQ Bai T Li Q Yang N Nan JX 《Chemico-biological interactions》2012,195(3):215-223
The purpose of the study was to investigate the anti-fibrotic effect and the potential mechanisms of action of betulinic acid (BA) against hepatic fibrosis in vivo and in vitro. BA is an active compound isolated from the bark of the birch tree Betula spp. (Betulaceae). Liver fibrosis was induced by intraperitoneal injections of thioacetamide (TAA, 200mg/kg) twice weekly for 6weeks in Wistar rats. The administration of BA (20 or 50mg/kg) was started following TAA injections and was continued for 6 or 8weeks to evaluate both the preventive and the protective effects. BA demonstrated great efficacy in preventing and curing hepatic fibrosis via attenuating the TAA-mediated increases in liver tissue hydroxyproline and α-smooth muscle actin (α-SMA). In vitro, BA effectively decreased the HSC-T6 cell viability induced by TNF-α and showed low toxicity in normal human chang liver cells. Moreover, BA significantly attenuated the expression of α-SMA and tissue inhibitor of metalloproteinase-1 (TIMP-1) and increased the levels of matrix metalloprotease (MMP)-13. BA also inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and the activation of nuclear factor-κB (NF-κB) in a time-dependent manner. This study provides evidence that BA exerts a significant anti-fibrosis effect by modulating the TLR4/MyD88/NF-κB signaling pathway. 相似文献
139.
热休克蛋白60(HSP60)是一种维持线粒体蛋白正常结构和功能的分子伴侣。该文克隆了梅氏新贝尼登虫HSP60基因cDNA序列(NmHSP60),并采用荧光定量RT-PCR和Western blot研究其在不同温度和盐度下的表达变化。以25℃为参照,18℃时,NmHSP60在虫卵和成虫中均表达下调;而32℃时,在成虫中表达上调。以盐度24为参照,盐度18时,NmHSP60在成虫中表达下调;盐度30时,在虫卵中表达上调。该结果揭示NmHSP60可能在梅氏新贝尼登虫应对环境应激中起重要作用。 相似文献
140.
A possible structure of retrograded maize starch speculated by UV and IR spectra of it and its components 总被引:3,自引:0,他引:3
Lian X Zhang K Luo Q Wang C Liu X 《International journal of biological macromolecules》2012,50(1):119-124
“Retrogradation” has been used to describe the changes that occur in starch after gelatinization, from an initially amorphous state to a more ordered or crystalline state, which has a significant impact on starch application in food, textiles and materials fields. But mechanism of starch retrogradation is still unclear until now and there is no breakthrough in this area. Here we are speculating a possible structure of retrograded maize starch by UV (binding with iodine) and IR spectra of it and its compositions. We speculate that nucleation of retrograded starch origins from combination of reducing end of amylopectin and non-reducing end of amylose, and retrogradation terminates at combining of non-reducing end of amylopectin and reducing end of amylose. The chain length of resistant digestion retrograded starch should be nearly same. The hydroxyl associated with sixth carbon atoms of glucan must form hydrogen bond with other hydroxyl of starch. 相似文献