全文获取类型
收费全文 | 8246篇 |
免费 | 207篇 |
国内免费 | 96篇 |
出版年
2023年 | 46篇 |
2022年 | 58篇 |
2021年 | 89篇 |
2020年 | 121篇 |
2019年 | 115篇 |
2018年 | 150篇 |
2017年 | 84篇 |
2016年 | 99篇 |
2015年 | 163篇 |
2014年 | 347篇 |
2013年 | 448篇 |
2012年 | 279篇 |
2011年 | 654篇 |
2010年 | 504篇 |
2009年 | 570篇 |
2008年 | 503篇 |
2007年 | 467篇 |
2006年 | 484篇 |
2005年 | 450篇 |
2004年 | 495篇 |
2003年 | 249篇 |
2002年 | 275篇 |
2001年 | 115篇 |
2000年 | 139篇 |
1999年 | 142篇 |
1998年 | 184篇 |
1997年 | 95篇 |
1996年 | 127篇 |
1995年 | 204篇 |
1994年 | 113篇 |
1993年 | 76篇 |
1992年 | 91篇 |
1991年 | 54篇 |
1990年 | 62篇 |
1989年 | 41篇 |
1988年 | 41篇 |
1987年 | 41篇 |
1986年 | 32篇 |
1985年 | 40篇 |
1984年 | 45篇 |
1983年 | 28篇 |
1982年 | 52篇 |
1981年 | 26篇 |
1980年 | 37篇 |
1979年 | 32篇 |
1978年 | 17篇 |
1977年 | 10篇 |
1976年 | 16篇 |
1975年 | 10篇 |
1972年 | 8篇 |
排序方式: 共有8549条查询结果,搜索用时 15 毫秒
1.
Residue Histidine 50 Plays a Key Role in Protecting α-Synuclein from Aggregation at Physiological pH
Ying-Chih Chi Geoffrey S. Armstrong David N. M. Jones Elan Z. Eisenmesser Chang-Wei Liu 《The Journal of biological chemistry》2014,289(22):15474-15481
α-Synuclein (αSyn) aggregation is involved in the pathogenesis of Parkinson disease (PD). Recently, substitution of histidine 50 in αSyn with a glutamine, H50Q, was identified as a new familial PD mutant. Here, nuclear magnetic resonance (NMR) studies revealed that the H50Q substitution causes an increase of the flexibility of the C-terminal region. This finding provides direct evidence that this PD-causing mutant can mediate long range effects on the sampling of αSyn conformations. In vitro aggregation assays showed that substitution of His-50 with Gln, Asp, or Ala promotes αSyn aggregation, whereas substitution with the positively charged Arg suppresses αSyn aggregation. Histidine carries a partial positive charge at neutral pH, and so our result suggests that positively charged His-50 plays a role in protecting αSyn from aggregation under physiological conditions. 相似文献
2.
3.
Xiaolei Zhuang Elena Semenova Dragan Maric Robert Craigie 《The Journal of biological chemistry》2014,289(2):1119-1127
Barrier-to-autointegration factor (BAF or BANF1) is highly conserved in multicellular eukaryotes and was first identified for its role in retroviral DNA integration. Homozygous BAF mutants are lethal and depletion of BAF results in defects in chromatin segregation during mitosis and subsequent nuclear envelope assembly. BAF exists both in phosphorylated and unphosphorylated forms with phosphorylation sites Thr-2, Thr-3, and Ser-4, near the N terminus. Vaccinia-related kinase 1 is the major kinase responsible for phosphorylation of BAF. We have identified the major phosphatase responsible for dephosphorylation of Ser-4 to be protein phosphatase 4 catalytic subunit. By examining the cellular distribution of phosphorylated BAF (pBAF) and total BAF (tBAF) through the cell cycle, we found that pBAF is associated with the core region of telophase chromosomes. Depletion of BAF or perturbing its phosphorylation state results not only in nuclear envelope defects, including mislocalization of LEM domain proteins and extensive invaginations into the nuclear interior, but also impaired cell cycle progression. This phenotype is strikingly similar to that seen in cells from patients with progeroid syndrome resulting from a point mutation in BAF. 相似文献
4.
《Cell》2022,185(17):3201-3213.e19
5.
Jeanet ConradieGert J. Lamprecht Stefanus OttoJannie C. Swarts 《Inorganica chimica acta》2002,328(1):191-203
The synthesis of new β-diketonato rhodium(I) complexes of the type [Rh(FcCOCHCOR)(CO)2] and [Rh(FcCOCHCOR)(CO)(PPh3)] with Fc=ferrocenyl and R=Fc, C6H5, CH3 and CF3 are described. 1H, 13C and 31P NMR data showed that for each of the non-symmetric β-diketonato mono-carbonyl rhodium(I) complexes, two isomers exist in solution. The equilibrium constant, Kc, which relates these two isomers in an equilibrium reaction, are concentration independent but temperature and solvent dependent. ΔrG, ΔrH and ΔrS values for this equilibrium have been determined and a linear relationship between solvent polarity on the Dimroth scale and Kc exists. The relationship between RhP bond lengths, d(RhP), and 31P NMR peak positions as well as coupling constants 1J(31P103Rh) has been quantified to allow calculation of approximate d(RhP) values. Variations in d(RhP) for [Rh(RCOCHCOR′)(CO)(PPh3)] complexes have also been related to the group electronegativities (Gordy scale) of the terminal β-diketonato R groups trans to PPh3. A measure of the electron density on the rhodium centre of [Rh(RCOCHCOR′)(CO)(PPh3)] may be expressed in terms of the IR carbonyl stretching wave number, ν(CO), the sum of the group electronegativities of the R and R′ groups, (χR+χR′), or the observed pKa′ values of the free β-diketones RCOCH2COR′. An empirical relationship between ν(CO) and either pKa′ or (χR+χR′) has also been quantified. 相似文献
6.
The synthesis and characterization of rare-earth (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu and Y) thiocyanate adducts with tripiperidinophosphine oxide (tpppO) with general formula (RE)(SCN)3(tpppO)3 are reported. Conductance measurements in acetonitrile indicate the non-electrolytic nature of the complexes. Infrared absorption spectra evidence that the SCN− ion coordinates through the nitrogen atom (isothiocyanate form) and that tpppO coordinates through the phosphoryl oxygen. X-ray powder patterns suggest the existence of three different crystal forms: (1) La; (2) an isomorphous series including Ce, Nd and Pr; and (3) another isomorphous series, including Sm, Gd, Eu, Ho, Er, Tb, Lu and Y. The visible spectra of the Nd adduct and the calculated parameters β = 0.98, b1/2 = 0.072 and δ = 1.06 indicate that the metal-ligand bonds are essentially electrostactic. The emission spectra of the Eu compound showed 5D0 → 7FJ bands (J = 0, 1, 2), suggesting a C3v symmetry for the coordination polyhedron. The lifetime of the 5D0 state is 1.28 ms. The emission spectra of the Tb complex presented 5D4 → 7FJ bands (J = 4, 5, 6) and the Dy complex showed the 4F9/2 → 6H13/2 band. The structure of the Pr complex showed that the coordination polyhedron is a trigonal antiprism, with the isothiocyanate anions in one base and three tpppO ligands in the other. Thermal analyses (TG-DTG) were carried out for the Ce, Nd and Gd adducts. Mass losses start between 250 and 334 °C. The final residues at 1300 °C are the corresponding phosphates. 相似文献
7.
Sotiris K. Hadjikakou Constantinos D. Antoniadis Maciej Kubicki Spyros Karkabounas 《Inorganica chimica acta》2005,358(10):2861-2866
A novel water stable, antimony(III) complex with the heterocyclic thioamide; 2-mercapto-pyrimidine (pmtH), of formula [Sb(pmt)3] · 0.5(CH3OH), has been synthesized and characterized by elemental analysis, 1H, 13C NMR and FT-IR spectroscopic techniques. Crystal structure of the molecule has been determined by X-ray diffraction at ambient conditions. The compound [C12H9N6S3Sb · 0.5(CH3OH)] is monoclinic, space group P21/c, a = 7.0646(7), b = 16.3767(14), c = 14.7265(13) Å, β = 92.016(7)°, Z = 4. In complex, three sulfur and three nitrogen atoms from thione ligands form a distorted pendagonal pyramidal geometry around antimony(III). The toxicity of the compound against tumor pleiomorphic cells, which has been isolated from a leiomyosarcoma tumor in the Wistar rat (chemical carcinogenesis using BaP) was studied in vitro. The results show that the compound did not destroy or prevent multiplication in vitro in leiomyosarcoma cells in low doses. The influence of the compound in the platelet aggregation, which correlates with the above tumor cells enhanced metastatic potential, has also been studied. The anti-metastatic capability study shows that the compound inhibited cancer cell induced aggregation up to the value of 10% in all mM concentrations tested. 相似文献
8.
《Journal of molecular biology》2021,433(4):166812
Spindly is a dynein adaptor involved in chromosomal segregation during cell division. While Spindly's N-terminal domain binds to the microtubule motor dynein and its activator dynactin, the C-terminal domain (Spindly-C) binds its cargo, the ROD/ZW10/ZWILCH (RZZ) complex in the outermost layer of the kinetochore. In humans, Spindly-C binds to ROD, while in C. elegans Spindly-C binds to both Zwilch (ZWL-1) and ROD-1. Here, we employed various biophysical techniques to characterize the structure, dynamics and interaction sites of C. elegans Spindly-C. We found that despite the overall disorder, there are two regions with variable α-helical propensity. One of these regions is located in the C-terminal half and is compact; the second is sparsely populated in the N-terminal half. The interactions with both ROD-1 and ZWL-1 are mostly mediated by the same two sequentially remote disordered segments of Spindly-C, which are C-terminally adjacent to the helical regions. The findings suggest that the Spindly-C binding sites on ROD-1 in the ROD-1/ZWL-1 complex context are either shielded or conformationally weakened by the presence of ZWL-1 such that only ZWL-1 directly interacts with Spindly-C in C. elegans 相似文献
9.
10.
The preferred mechanisms of racemization for three tris chelate complexes, Co(acac)3, Fe(phen)3 3+ and Fe[S2CN(CH2)4]3, were investigated by molecular modeling. The transition states for both a Bailar twist and a Rây-Dutt twist were considered; semi-empirical calculations (PM3) yielded activation energies. The preferred mechanism was the Bailar twist for Co(acac)3 and Fe[S2CN(CH2)4]3 with activation energies of 83.2 and 7.3 kcal mol−1, respectively, and the Rây-Dutt twist for Fe(phen)3 3+ with an activation energy of 114.4 kcal mol−1. These results are compared with those of geometrical models. 相似文献