全文获取类型
收费全文 | 635篇 |
免费 | 50篇 |
国内免费 | 1篇 |
专业分类
686篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 5篇 |
2020年 | 7篇 |
2019年 | 23篇 |
2018年 | 23篇 |
2017年 | 16篇 |
2016年 | 26篇 |
2015年 | 29篇 |
2014年 | 20篇 |
2013年 | 30篇 |
2012年 | 46篇 |
2011年 | 40篇 |
2010年 | 24篇 |
2009年 | 25篇 |
2008年 | 29篇 |
2007年 | 53篇 |
2006年 | 39篇 |
2005年 | 54篇 |
2004年 | 40篇 |
2003年 | 35篇 |
2002年 | 40篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 7篇 |
1997年 | 1篇 |
1996年 | 7篇 |
1995年 | 10篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 4篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有686条查询结果,搜索用时 11 毫秒
21.
22.
Sarcoplasmic reticulum (SR) is abundant in uterine smooth muscle cells. The functional role of this organelle in the regulation of uterine myocytes is not fully understood. The data available in the literature suggest that SR plays a dual role: as a source of calcium and as a calcium sink shaping calcium transients produced by membrane depolarisation and uterotonic agonists. Advances in digital imaging techniques including confocal microscopy of isolated living cells, and the development of methods for direct measurement of intraluminal calcium, has triggered a substantial increase in the number of publications elucidating the role of intracellular stores in calcium signalling. In this paper we review the literature and our own work on the SR calcium store in uterine smooth muscle cells. 相似文献
23.
Eron JN Miller NV Badakva AM 《Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology》2004,11(2):P31-P32
The gaze fixation reaction was studied in three rhesus monkeys before and during thermoneutral (34.5 degrees C) water immersion to the mid-chest level. The angular vestibulo-ocular reflex gain increased and the head angular velocity decreased significantly in all monkeys in 5 h after the start of immersion. Additionally, one animal was immersed to the neck level. Two hours in the condition of more pronounced support deprivation decreased significantly angular velocity of the head but not increased the angular vestibulo-ocular reflex gain. Therefore, support deprivation act upon the head movement control first. 相似文献
24.
25.
The interaction of the second and third AT-hooks of HMGA1 (formerly HMGI/Y), which bind selectively in the minor groove of an AT-rich DNA sequence, was studied at different temperatures and ionic strengths by spectropolarimetry, spectrofluorimetry, isothermal titration calorimetry and differential scanning calorimetry. The data show that binding of the ten amino acid core element of the two AT-hooks, which penetrates deep into the minor groove, is entropically driven: both the entropy and enthalpy of association of the peptides to the target DNA are positive up to 50 degrees C. The seven amino acid extension of the core in the second AT-hook, which extends out from the minor groove and loops over the phosphodiester backbone, adds a substantial negative enthalpic component into the binding of the 17 residue DBD2 peptide to DNA that corresponds in magnitude to the enthalpy of formation of two hydrogen bonds. The ionic strength dependence of the association constant allowed an estimation of the electrostatic component of binding and, by subtraction, the contribution of the non-electrostatic component, which results from dehydration of the contacting surfaces and makes up almost 70% of the total energy of complex formation. The exceptionally large positive entropy and enthalpy of association of the core AT-hook peptides with target DNA suggest that the water, which is removed from the minor groove of DNA upon binding, is in a highly ordered state. Acetylation of the lysine residue in the second AT-hook, which corresponds to Lys65 of HMGA1, has little effect on the DNA binding; so it appears that repression of the hIFNbeta gene, which follows this modification, is not a direct result of the abrogation of DNA binding. 相似文献
26.
Liepinsh E Leonchiks A Sharipo A Guignard L Otting G 《Journal of molecular biology》2003,326(1):217-223
The R3H domain is a conserved sequence motif, identified in over 100 proteins, that is thought to be involved in polynucleotide-binding, including DNA, RNA and single-stranded DNA. In this work the 3D structure of the R3H domain from human Smubp-2 was determined by NMR spectroscopy. It is the first 3D structure determination of an R3H domain. The fold presents a small motif, consisting of a three-stranded antiparallel beta-sheet and two alpha-helices, which is related to the structures of the YhhP protein and the C-terminal domain of the translational initiation factor IF3. The similarities are non-trivial, as the amino acid identities are below 10%. Three conserved basic residues cluster on the same face of the R3H domain and could play a role in nucleic acid recognition. An extended hydrophobic area at a different site of the molecular surface could act as a protein-binding site. A strong correlation between conservation of hydrophobic amino acids and side-chain solvent protection indicates that the structure of the Smubp-2 R3H domain is representative of R3H domains in general. 相似文献
27.
Mitochondrial production of reactive oxygen species (ROS) at Complex I of the electron transport chain is implicated in the etiology of neural cell death in acute and chronic neurodegenerative disorders. However, little is known regarding the regulation of mitochondrial ROS production by NADH-linked respiratory substrates under physiologically realistic conditions in the absence of respiratory chain inhibitors. This study used Amplex Red fluorescence measurements of H2O2 to test the hypothesis that ROS production by isolated brain mitochondria is regulated by membrane potential (DeltaPsi) and NAD(P)H redox state. DeltaPsi was monitored by following the medium concentration of the lipophilic cation tetraphenylphosphonium with a selective electrode. NAD(P)H autofluorescence was used to monitor NAD(P)H redox state. While the rate of H2O2 production was closely related to DeltaPsi and the level of NAD(P)H reduction at high values of DeltaPsi, 30% of the maximal rate of H2O2 formation was still observed in the presence of uncoupler (p-trifluoromethoxycarbonylcyanide phenylhydrazone) concentrations that provided for maximum depolarization of DeltaPsi and oxidation of NAD(P)H. Our findings indicate that ROS production by mitochondria oxidizing physiological NADH-dependent substrates is regulated by DeltaPsi and by the NAD(P)H redox state over ranges consistent with those that exist at different levels of cellular energy demand. 相似文献
28.
Martsev SP Dubnovitsky AP Vlasov AP Hoshino M Hasegawa K Naiki H Goto Y 《Biochemistry》2002,41(10):3389-3395
The recombinant V(L) domain that represents the variable part of the light chain (type kappa) of mouse monoclonal antibody F11 directed against human spleen ferritin was found to form amyloid fibrils at acidic pH as evidenced by electron microscopy, thioflavin T binding, and apple-green birefringence after Congo red staining. This is the first demonstration of amyloid fibril formation of the mouse V(L) domain. To understand the mechanism of acidic pH-induced amyloid fibril formation, conformational changes of the V(L) domain were studied by one-dimensional NMR, differential scanning calorimetry, analytical ultracentrifugation, hydrophobic dye binding, far-UV circular dichroism, and tryptophan fluorescence. The results indicated accumulation of two intermediate states during acid unfolding, which might be responsible for amyloid fibril formation. The more structured intermediate that exhibited maximal accumulation at pH 3 retained the nativelike secondary structure and a hydrophobic core, but exposed hydrophobic surfaces that bind 8-anilino-1-naphthalenesulfonate. Below pH 2, a more disordered intermediate with dequenched tryptophan fluorescence but still retaining the beta-sheet structure accumulated. The optimal pH of amyloid fibril formation (i.e., pH 4) was close to the optimal pH of the accumulation of the nativelike intermediate, suggesting that the amyloid fibrils might be formed through this intermediate. 相似文献
29.
Abnormal accumulation of Ca2+ and exposure to pro-apoptotic proteins, such as Bax, is believed to stimulate mitochondrial generation of reactive oxygen species (ROS) and contribute to neural cell death during acute ischemic and traumatic brain injury, and in neurodegenerative diseases, e.g. Parkinson's disease. However, the mechanism by which Ca2+ or apoptotic proteins stimulate mitochondrial ROS production is unclear. We used a sensitive fluorescent probe to compare the effects of Ca2+ on H2O2 emission by isolated rat brain mitochondria in the presence of physiological concentrations of ATP and Mg2+ and different respiratory substrates. In the absence of respiratory chain inhibitors, Ca2+ suppressed H2O2 generation and reduced the membrane potential of mitochondria oxidizing succinate, or glutamate plus malate. In the presence of the respiratory chain Complex I inhibitor rotenone, accumulation of Ca2+ stimulated H2O2 production by mitochondria oxidizing succinate, and this stimulation was associated with release of mitochondrial cytochrome c. In the presence of glutamate plus malate, or succinate, cytochrome c release and H2O2 formation were stimulated by human recombinant full-length Bax in the presence of a BH3 cell death domain peptide. These results indicate that in the presence of ATP and Mg2+, Ca2+ accumulation either inhibits or stimulates mitochondrial H2O2 production, depending on the respiratory substrate and the effect of Ca2+ on the mitochondrial membrane potential. Bax plus a BH3 domain peptide stimulate H2O2 production by brain mitochondria due to release of cytochrome c and this stimulation is insensitive to changes in membrane potential. 相似文献
30.