全文获取类型
收费全文 | 2528篇 |
免费 | 144篇 |
国内免费 | 89篇 |
专业分类
2761篇 |
出版年
2024年 | 3篇 |
2023年 | 19篇 |
2022年 | 24篇 |
2021年 | 33篇 |
2020年 | 33篇 |
2019年 | 36篇 |
2018年 | 47篇 |
2017年 | 34篇 |
2016年 | 49篇 |
2015年 | 54篇 |
2014年 | 114篇 |
2013年 | 155篇 |
2012年 | 130篇 |
2011年 | 161篇 |
2010年 | 131篇 |
2009年 | 88篇 |
2008年 | 132篇 |
2007年 | 101篇 |
2006年 | 95篇 |
2005年 | 109篇 |
2004年 | 97篇 |
2003年 | 94篇 |
2002年 | 93篇 |
2001年 | 57篇 |
2000年 | 35篇 |
1999年 | 49篇 |
1998年 | 89篇 |
1997年 | 80篇 |
1996年 | 52篇 |
1995年 | 53篇 |
1994年 | 56篇 |
1993年 | 49篇 |
1992年 | 35篇 |
1991年 | 33篇 |
1990年 | 33篇 |
1989年 | 30篇 |
1988年 | 26篇 |
1987年 | 27篇 |
1986年 | 15篇 |
1985年 | 32篇 |
1984年 | 46篇 |
1983年 | 32篇 |
1982年 | 38篇 |
1981年 | 16篇 |
1980年 | 15篇 |
1979年 | 12篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1973年 | 3篇 |
排序方式: 共有2761条查询结果,搜索用时 0 毫秒
31.
Xiaogang Gu John Glushka Yanbin Yin Ying Xu Timothy Denny James Smith Yingnan Jiang Maor Bar-Peled 《The Journal of biological chemistry》2010,285(12):9030-9040
The UDP-sugar interconverting enzymes involved in UDP-GlcA metabolism are well described in eukaryotes but less is known in prokaryotes. Here we identify and characterize a gene (RsU4kpxs) from Ralstonia solanacearum str. GMI1000, which encodes a dual function enzyme not previously described. One activity is to decarboxylate UDP-glucuronic acid to UDP-β-l-threo-pentopyranosyl-4″-ulose in the presence of NAD+. The second activity converts UDP-β-l-threo-pentopyranosyl-4″-ulose and NADH to UDP-xylose and NAD+, albeit at a lower rate. Our data also suggest that following decarboxylation, there is stereospecific protonation at the C5 pro-R position. The identification of the R. solanacearum enzyme enables us to propose that the ancestral enzyme of UDP-xylose synthase and UDP-apiose/UDP-xylose synthase was diverged to two distinct enzymatic activities in early bacteria. This separation gave rise to the current UDP-xylose synthase in animal, fungus, and plant as well as to the plant Uaxs and bacterial ArnA and U4kpxs homologs. 相似文献
32.
Vibrational circular dichroism (VCD) spectroscopy was used to investigate the solution conformations of cyclosporins A, C, D, G, and H in CDCl(3), in the amide I and NH/OH-stretching regions, and their corresponding magnesium complexes in CD(3)CN, in the amide I region. VCD spectra are sensitive to the chiral arrangement of Cdbond;O and NH bonds in this cyclic undecapeptide. Calculations of molecular geometries, as well as IR and VCD intensities of model cyclosporin fragments that include the intramolecular hydrogen bonds of the crystal conformations of cyclosporins A and H (CsA and CsH), were carried out at the density functional theory (DFT; BPW91 functional/6-31G* basis set) level. The good agreement between IR and VCD spectra from experiment and DFT calculations provides evidence that the crystal conformation of CsA is dominant in CDCl(3) solution; CsH, however, assumes both an intramolecularly hydrogen-bonded crystal conformation and more open forms in solution. Comparisons of the experimental and calculated VCD spectra in the NH/OH-stretching region of the noncomplexed cyclosporins indicate that conformers with both free and hydrogen-bonded NH and OH groups are present in solution. Differences between the IR and VCD spectra for the metal-free and magnesium-complexed cyclosporins are indicative of strong interactions between cyclosporins and magnesium ions. 相似文献
33.
J?rg Willenborg Claudia Huber Anna Koczula Birgit Lange Wolfgang Eisenreich Peter Valentin-Weigand Ralph Goethe 《The Journal of biological chemistry》2015,290(9):5840-5854
Streptococcus suis is a neglected zoonotic pathogen that has to adapt to the nutritional requirements in the different host niches encountered during infection and establishment of invasive diseases. To dissect the central metabolic activity of S. suis under different conditions of nutrient availability, we performed labeling experiments starting from [13C]glucose specimens and analyzed the resulting isotopologue patterns in amino acids of S. suis grown under in vitro and ex vivo conditions. In combination with classical growth experiments, we found that S. suis is auxotrophic for Arg, Gln/Glu, His, Leu, and Trp in chemically defined medium. De novo biosynthesis was shown for Ala, Asp, Ser, and Thr at high rates and for Gly, Lys, Phe, Tyr, and Val at moderate or low rates, respectively. Glucose degradation occurred mainly by glycolysis and to a minor extent by the pentose phosphate pathway. Furthermore, the exclusive formation of oxaloacetate by phosphoenolpyruvate (PEP) carboxylation became evident from the patterns in de novo synthesized amino acids. Labeling experiments with S. suis grown ex vivo in blood or cerebrospinal fluid reflected the metabolic adaptation to these host niches with different nutrient availability; however, similar key metabolic activities were identified under these conditions. This points at the robustness of the core metabolic pathways in S. suis during the infection process. The crucial role of PEP carboxylation for growth of S. suis in the host was supported by experiments with a PEP carboxylase-deficient mutant strain in blood and cerebrospinal fluid. 相似文献
34.
Hiroshi Nakagawa Hironari Kamikubo Mikio Kataoka 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(1):27-33
In order to examine the properties specific to the folded protein, the effect of the conformational states on protein dynamical transition was studied by incoherent elastic neutron scattering for both wild type and a deletion mutant of staphylococcal nuclease. The deletion mutant of SNase which lacks C-terminal 13 residues takes a compact denatured structure, and can be regarded as a model of intrinsic unstructured protein. Incoherent elastic neutron scattering experiments were carried out at various temperature between 10 K and 300 K on IN10 and IN13 installed at ILL. Temperature dependence of mean-square displacements was obtained by the q-dependence of elastic scattering intensity. The measurements were performed on dried and hydrated powder samples. No significant differences were observed between wild type and the mutant for the hydrated samples, while significant differences were observed for the dried samples. A dynamical transition at ∼ 140 K observed for both dried and hydrated samples. The slopes of the temperature dependence of MSD before transition and after transition are different between wild type and the mutant, indicating the folding induces hardening. The hydration water activates a further transition at ∼ 240 K. The behavior of the temperature dependence of MSD is indistinguishable for wild type and the mutant, indicating that hydration water dynamics dominate the dynamical properties. 相似文献
35.
36.
37.
Phytochromes are molecular light switches by virtue of their photochromic red/far-red reversibility. The His-324 residue next to the chromophore-linked Cys-323 plays a critical role in conferring photochromism to the tetrapyrrole chromophore in native phytochrome A. The chromophore appears to be enclosed between the amphiphilic α-helical chains in a hydrophobic pocket. The absorbance maxima of both the Pr and the Pfr forms of pea phytochrome A are blue-shifted by 10 and 20 nm, respectively, upon C-terminal truncation. We speculate that the quaternary structure of the phytochrome A molecule involves some interactions of the C-terminal half with the chromophore domain. The Pfr conformation of phytochrome includes an amphiphilic α-helix of the amino terminal chain, which occurs in 113 ms after picosecond photoisomerization of the Pr form. Compared to α-helical folding, unfolding of the α-helix occurs faster in about 310 μs upon phototransformation of the Pfr form of phytochrome A. The photochromic transformation of phytochrome A modulates protein kinase-catalysed phosphorylation sites in vivo and in vitro, but only a subtle local change in conformation is detectable in the phosphorylated phytochromes. This suggests that the post-translational modification serves as a surface label, rather than a transducer-activating trigger, for the recognition of a putative phytochrome receptor. 相似文献
38.
The cyanobacterium Oscillatoria agardhii was grown in continuous culture under various light conditions in order to study the interactions of light on phosphorus-limited growth. Under severe P-limiting (light-saturating) conditions, a low chlorophyll a and C-phycocyanin content was found. In addition, the light-harvesting capacity, reflected in the values of P
max (maximum light-saturated oxygen production rate) and (photosynthetic affinity), were low compared to light-limited cultures.Reduction of the light climate, either by reduction of the length of the photoperiod or light-intensity, resulted in an increase in light-harvesting capacity (higher pigment content, P
m and ) during growth under P-limiting conditions. Light-induced changes in P
max and could be related to the relative growth rate, being the actual growth rate as a fraction of the growth rate which would be observed under light-limiting conditions.Under P-limiting conditions, reduction of the light-climate caused a reduction in dry weight of the culture. This decrease was mainly due to a decrease in carbohydrate content of the cells. Under all conditions tested, carbohydrates were found to accumulate during the light-period and to be consumed during the dark-period.Evaluation of carbohydrate consumption in the dark yielded a specific maintenance rate constant of 0.001 h-1. This observation leads to the conclusion that the specific maintenance rate constant is independent on the character of the growth rate limiting nutrient for O. agardhii. 相似文献
39.
40.
Using steady-state fluorescence and nanosecond time-resolved fluorescence techniques, the Ca 2 -ATPase conformational changes induced by ganglioside GM3 were studied with different quenchers. The results showed that GM3 could significantly increase the lifetime of intrinsic fluorescence of Ca2 -ATPase reconstituted into proteoliposomes, and could also weaken the intrinsic fluorescence quenching by KI or hypocrellin B, HB. Further-more, by using quenching kinetic analysis of the time-resolved fluorescence, in the presence of GM3, the quenching constant (Ksv) and quenching efficiency were significantly lowered. The obtained results suggest that the oligosaccha-ride chain and the ceramide moieties of the GM3 molecule could interact with its counterparts of the Ca2 -ATPase re-spectively, thus change the conformation of the hydrophobic domain of the enzyme, making the tryptophan residues in different regions shift towards the hydrophilic-hydrophobic interface, and hence shorten the distance between the hy 相似文献