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71.
Follicle‐stimulating hormone promotes age‐related endometrial atrophy through cross‐talk with transforming growth factor beta signal transduction pathway 下载免费PDF全文
Dan Zhang Jingyi Li Gufeng Xu Runjv Zhang Chengliang Zhou Yeqing Qian Yifeng Liu Luting Chen Bo Zhu Xiaoqun Ye Fan Qu Xinmei Liu Shuai Shi Weijun Yang Jianzhong Sheng Hefeng Huang 《Aging cell》2015,14(2):284-287
It is widely believed that endometrial atrophy in postmenopausal women is due to an age‐related reduction in estrogen level. But the role of high circulating follicle‐stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here, we explored the role of high circulating FSH in physiological endometrial atrophy. We found that FSH exacerbated post‐OVX endometrial atrophy in mice, and this effect was ameliorated by lowering FSH with Gonadotrophin‐releasing hormone agonist (GnRHa). In vitro, FSH inhibited endometrial proliferation and promoted the apoptosis of primary cultured endometrial cells in a dose‐dependent manner. In addition, upregulation of caspase3, caspase8, caspase9, autophagy‐related proteins (ATG3, ATG5, ATG7, ATG12 and LC3) and downregulation of c‐Jun were also observed in endometrial adenocytes. Furthermore, smad2 and smad3 showed a time‐dependent activation in endometrial cells which can be partly inhibited by blocking the transforming growth factor beta receptor II (TβRII). In conclusion, FSH regulated endometrial atrophy by affecting the proliferation, autophagy and apoptosis of endometrial cells partly through activation of the transforming growth factor beta (TGFβ) pathway. 相似文献
72.
A "dual-layer membrane cloaking" (DLMC) method was developed to construct disposable electrochemical immunosensor for direct determination of serum sample. Mouse IgG (MIgG) molecules were firstly immobilized on a substrate. After the formation of a didodecyldimethylammonium bromide (DDAB) membrane on the MIgG modified substrate, an additional bovine serum albumin (BSA) thin layer was formed to build a BSA/DDAB dual-layer membrane (DLM). When alkaline phosphatase conjugated anti-mouse IgG antibodies (anti-MIgG-ALP) in human serum were incubated on the substrate, anti-MIgG-ALP was recognized specifically by the immobilized MIgG while all nonspecifically adsorbed proteins were selectively removed together with BSA/DDAB DLM by 5% Triton X-100 (v/v) before final measurements. The BSA/DDAB DLM was characterized and optimized by surface plasmon resonance (SPR) technique, and further employed in a disposable immunoassay based on an ITO chip. Under optimal conditions, MIgG in human serum was directly detected in the range of 2.0-18.0 ng mL(-1) without dilution or separation. A limit of detection as low as 0.922 ng mL(-1) (6.15 pM) was obtained. The proposed DLMC method can efficiently prevent the penetration of matrix proteins through single cloaking membrane and completely eliminate nonspecific adsorption. It has great potential in providing a versatile way for direct determination of serum sample with ultra-sensitivity. 相似文献
73.
Foo LC Allen NJ Bushong EA Ventura PB Chung WS Zhou L Cahoy JD Daneman R Zong H Ellisman MH Barres BA 《Neuron》2011,71(5):799-811
The inability to purify and culture astrocytes has long?hindered studies of their function. Whereas astrocyte progenitor cells can be cultured from neonatal brain, culture of mature astrocytes from postnatal brain has not been possible. Here, we report a new method to prospectively purify astrocytes by immunopanning. These astrocytes undergo apoptosis in culture, but vascular cells and HBEGF promote their survival in serum-free culture. We found that some developing astrocytes normally undergo apoptosis in?vivo and that the vast majority of astrocytes contact blood vessels, suggesting that?astrocytes are matched to blood vessels by competing for vascular-derived trophic factors such as HBEGF. Compared to traditional astrocyte cultures, the gene profiles of the cultured purified postnatal astrocytes much more closely resemble those of in?vivo astrocytes. Although these astrocytes strongly promote synapse formation and function, they do not secrete glutamate in response to stimulation. 相似文献
74.
Wang D Zong C Koag MC Wang Y Drews O Fang C Scruggs SB Ping P 《Molecular & cellular proteomics : MCP》2011,10(5):M110.006122
Myocardial proteasomes are comprised of 20S core particles and 19S regulatory particles, which together carry out targeted degradation of cardiac proteins. The 19S complex is unique among the regulators of proteasomes in that it affects both the capacity and specificity of protein degradation. However, a comprehensive molecular characterization of cardiac 19S complexes is lacking. In this investigation, we tailored a multidimensional chromatography-based purification strategy to isolate structurally intact and functionally viable 19S complexes from murine hearts. Two distinct subpopulations of 19S complexes were isolated based upon (1) potency of activating 20S proteolytic activity, and (2) molecular composition using a combination of immuno-detection, two-dimensional-differential gel electrophoresis, and MS-based approaches. Heat shock protein 90 (Hsp90) was identified to be characteristic to 19S subpopulation I. The physical interaction of Hsp90 with 19S complexes was demonstrated via multiple approaches. Inhibition of Hsp90 activity using geldanamycin or BIIB021 potentiated the ability of subpopulation I to activate 20S proteasomes in the murine heart, thus demonstrating functional specificity of Hsp90 in subpopulation I. This investigation has advanced our understanding of the molecular heterogeneity of cardiac proteasomes by identifying molecularly and functionally distinct cardiac 19S complexes. The preferential association of Hsp90 with 19S subpopulation I unveils novel targets for designing proteasome-based therapeutic interventions for combating cardiac disease. 相似文献
75.
Chen J Li Q Zhang Y Yang P Zong Y Qu S Liu Z 《Journal of physiology and biochemistry》2011,67(2):153-163
The reported data indicate that oleic acid (OA) decreases cholesterol absorption. To explore the underlying mechanisms, the
effects of OA on the expression of cholesterol transport-related proteins (NPC1L1, ABCG5/8, ACAT2, MTP) and the unfolded protein
response (UPR) pathway were studied in CaCo-2 enterocytes by incubating CaCo-2 cells with taurocholate micelles or taurocholate
micelles containing different concentrations of OA (0.25–1.0 mM). We show that OA effectively induces XBP1 mRNA splicing,
a key component of the UPR signaling, and the expression of BiP and mature ATF6 proteins in a concentration-dependent manner,
leading to the induction of endoplasmic reticulum (ER) stress and activation of the UPR. Interestingly, OA decreases NPC1L1
expression in a dose-dependent manner while it has no effects on ABCG5 and MTP mRNA level or SREBP-2, ABCG8, and ACAT2 protein
level. In CaCo-2 cells treated with 1.0 mM OA, both the NPC1L1 mRNA level and the NPC1L1 protein expression in brush-border
membrane fractions were decreased by 39% and 37%, respectively (P < 0.01). A dose of 1 mM dithiothreitol (DTT), a positive control for ER stress induction, also decreases NPC1L1 mRNA and
protein expression by 27% and 23%, respectively (P < 0.05). Furthermore, 4-phenyl-butyric acid, an UPR inhibitor, blocks OA- and DTT-induced reduction on NPC1L1 mRNA and protein
levels. The results suggest that OA down-regulates NPC1L1 mRNA and protein expression via the induction of the UPR, which
may play an important role in reducing intestinal cholesterol absorption. 相似文献
76.
Xin Zong Xiao Xiao Fu Jie Yuanzhi Cheng Mingliang Jin Yulong Yin Yizhen Wang 《中国科学:生命科学英文版》2021,(11):1988-1991
Dear editor,
Endotoxic shock usually results from infection-induced physiologic,pathologic,and biologic abnormalities (Singer et al.,2016).Undeniably,it is stil... 相似文献
77.
Synthesis of (R)-2-trimethylsilyl-2-hydroxyl-propionitrile via asymmetric transcyanation of acetyltrimethylsilane with acetone cyanohydrin in an aqueous/organic biphasic system catalyzed by (R)-hydroxynitrile lyase from Prunus japonica seed meal was successfully carried out for the first time. The optimal volume ratio of aqueous to organic phase, buffer pH value and reaction temperature were 15% (v/v), 5.0 and 30°C, respectively, under which both substrate conversion and product enantiomeric excess (ee) were 99%. Silicon atom in the substrate showed great effect on the reaction. Acetyltrimethylsilane was a much better substrate for (R)-hydroxynitrile lyase from Prunus japonica than its carbon analogue. 相似文献
78.
Moulick K Ahn JH Zong H Rodina A Cerchietti L Gomes DaGama EM Caldas-Lopes E Beebe K Perna F Hatzi K Vu LP Zhao X Zatorska D Taldone T Smith-Jones P Alpaugh M Gross SS Pillarsetty N Ku T Lewis JS Larson SM Levine R Erdjument-Bromage H Guzman ML Nimer SD Melnick A Neckers L Chiosis G 《Nature chemical biology》2011,7(11):818-826
Most cancers are characterized by multiple molecular alterations, but identification of the key proteins involved in these signaling pathways is currently beyond reach. We show that the inhibitor PU-H71 preferentially targets tumor-enriched Hsp90 complexes and affinity captures Hsp90-dependent oncogenic client proteins. We have used PU-H71 affinity capture to design a proteomic approach that, when combined with bioinformatic pathway analysis, identifies dysregulated signaling networks and key oncoproteins in chronic myeloid leukemia. The identified interactome overlaps with the well-characterized altered proteome in this cancer, indicating that this method can provide global insights into the biology of individual tumors, including primary patient specimens. In addition, we show that this approach can be used to identify previously uncharacterized oncoproteins and mechanisms, potentially leading to new targeted therapies. We further show that the abundance of the PU-H71-enriched Hsp90 species, which is not dictated by Hsp90 expression alone, is predictive of the cell's sensitivity to Hsp90 inhibition. 相似文献
79.
Huang Y Corbley MJ Tang Z Yang L Peng Y Zhang ZY Tong TJ 《Journal of cellular physiology》2004,201(3):483-491
It has been suggested that genes which exercise checkpoint control during cell cycle traverse are equally important to the process of apoptotic cell death. In this study, we show that the key cell cycle regulatory gene p21(WAF1) is also involved in the execution of apoptosis. p21(WAF1) expression was down-regulated during NaBu-induced apoptosis of senescent normal diploid human 2BS fibroblasts. Conversely, when p21(WAF1) expression was actively suppressed in 2BS cells by a stably transfected antisense p21(WAF1) construct, apoptosis was accelerated and senescence was delayed, as shown by several markers of cell aging. Down-regulation of p21(WAF1) by antisense caused an increase in the phosphorylation and inactivation of pRb. Phosphorylation of pRb was further enhanced upon induction of apoptosis by NaBu. Our results suggest that p21(WAF1), acting through the phosphorylation of pRb, regulates whether 2BS cells cease to proliferate and become senescent but resistant to apoptosis, or whether they accelerate proliferation while becoming more susceptible to apoptotic stimuli. 相似文献
80.
Two types of sulfated octyl tetra- to octaoligofucosides with different sulfation patterns were synthesized employing a combination of stepwise elongation and convergent strategies in which trichloroacetimidates and thioglycosides were selected as the glycosyl donors. 相似文献