全文获取类型
收费全文 | 15979篇 |
免费 | 1186篇 |
国内免费 | 5篇 |
专业分类
17170篇 |
出版年
2023年 | 56篇 |
2022年 | 192篇 |
2021年 | 331篇 |
2020年 | 164篇 |
2019年 | 235篇 |
2018年 | 295篇 |
2017年 | 269篇 |
2016年 | 471篇 |
2015年 | 801篇 |
2014年 | 874篇 |
2013年 | 1025篇 |
2012年 | 1384篇 |
2011年 | 1272篇 |
2010年 | 844篇 |
2009年 | 800篇 |
2008年 | 1014篇 |
2007年 | 1030篇 |
2006年 | 918篇 |
2005年 | 848篇 |
2004年 | 816篇 |
2003年 | 737篇 |
2002年 | 650篇 |
2001年 | 316篇 |
2000年 | 276篇 |
1999年 | 229篇 |
1998年 | 142篇 |
1997年 | 112篇 |
1996年 | 84篇 |
1995年 | 74篇 |
1994年 | 70篇 |
1993年 | 73篇 |
1992年 | 71篇 |
1991年 | 82篇 |
1990年 | 61篇 |
1989年 | 69篇 |
1988年 | 60篇 |
1987年 | 41篇 |
1986年 | 42篇 |
1985年 | 44篇 |
1984年 | 28篇 |
1983年 | 34篇 |
1982年 | 14篇 |
1981年 | 24篇 |
1979年 | 14篇 |
1978年 | 23篇 |
1977年 | 22篇 |
1976年 | 12篇 |
1974年 | 17篇 |
1973年 | 17篇 |
1972年 | 14篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
1.
The desulfurization activity of the resting cells of Gordona sp. CYKS1 was strongly depended on harvest time and the highest value when the cells had been harvested in the early growth phase (0.12 mg sulfur g–1 cell–1 h–1). For the model oil, hexadecane containing dibenzothiophene, the specific desulfurization rate decreased as the reaction proceeded. Both the specific and the volumetric desulfurization rates were not significantly affected by the aqueous-to-oil phase ratio. The diesel oils, light gas oil and a middle distillate unit feed were desulfurized at higher rates (ca. 0.34 mg sulfur g–1 cell–1 h–1) than the model oil (0.12 mg sulfur g–1 cell–1 h–1). 相似文献
2.
Julie K. De Zutter Kara B. Levine Di Deng Anthony Carruthers 《The Journal of biological chemistry》2013,288(28):20734-20744
The human blood-brain barrier glucose transport protein (GLUT1) forms homodimers and homotetramers in detergent micelles and in cell membranes, where the GLUT1 oligomeric state determines GLUT1 transport behavior. GLUT1 and the neuronal glucose transporter GLUT3 do not form heterocomplexes in human embryonic kidney 293 (HEK293) cells as judged by co-immunoprecipitation assays. Using homology-scanning mutagenesis in which GLUT1 domains are substituted with equivalent GLUT3 domains and vice versa, we show that GLUT1 transmembrane helix 9 (TM9) is necessary for optimal association of GLUT1-GLUT3 chimeras with parental GLUT1 in HEK cells. GLUT1 TMs 2, 5, 8, and 11 also contribute to a less abundant heterocomplex. Cell surface GLUT1 and GLUT3 containing GLUT1 TM9 are 4-fold more catalytically active than GLUT3 and GLUT1 containing GLUT3 TM9. GLUT1 and GLUT3 display allosteric transport behavior. Size exclusion chromatography of detergent solubilized, purified GLUT1 resolves GLUT1/lipid/detergent micelles as 6- and 10-nm Stokes radius particles, which correspond to GLUT1 dimers and tetramers, respectively. Studies with GLUTs expressed in and solubilized from HEK cells show that HEK cell GLUT1 resolves as 6- and 10-nm Stokes radius particles, whereas GLUT3 resolves as a 6-nm particle. Substitution of GLUT3 TM9 with GLUT1 TM9 causes chimeric GLUT3 to resolve as 6- and 10-nm Stokes radius particles. Substitution of GLUT1 TM9 with GLUT3 TM9 causes chimeric GLUT1 to resolve as a mixture of 6- and 4-nm particles. We discuss these findings in the context of determinants of GLUT oligomeric structure and transport function. 相似文献
3.
Molecular alteration of a muscarinic acetylcholine receptor system during synaptogenesis 总被引:7,自引:0,他引:7
T H Large N J Cho F G De Mello W L Klein 《The Journal of biological chemistry》1985,260(15):8873-8881
Biochemical properties of the muscarinic acetylcholine receptor system of the avian retina were found to change during the period when synapses form in ovo. Comparison of ligand binding to membranes obtained before and after synaptogenesis showed a significant increase in the affinity, but not proportion, of the high affinity agonist-binding state. There was no change in receptor sensitivity to antagonists during this period. Pirenzepine binding, which can discriminate muscarinic receptor subtypes, showed the presence of a single population of low affinity sites (M2) before and after synaptogenesis. The change in agonist binding was not due to the late development of receptor function; tests for receptor-stimulated phosphatidylinositol turnover and for modulation of agonist binding by guanylylimidodiphosphate showed functional coupling to be present several days prior to the onset of synapse formation. However, detergent-solubilization of membranes eliminated differences in agonist binding between receptors from embryos and hatched chicks, suggesting a developmental change in interactions of the receptor with functionally related membrane components. A possible basis for altered interactions was obtained from isoelectric point data showing that the muscarinic receptor population underwent a transition from a predominantly low pI form (4.25) in 13 day embryos to a predominantly high pI form (4.50) in newly hatched chicks. The possibility that biochemical changes in the muscarinic receptor play a role in differentiation of the system by controlling receptor position on the surface of nerve cells is discussed. 相似文献
4.
Julie A. Harris Akihiko Koyama Sumihiro Maeda Kaitlyn Ho Nino Devidze Dena B. Dubal Gui-Qiu Yu Eliezer Masliah Lennart Mucke 《PloS one》2012,7(9)
Accumulation of hyperphosphorylated tau in the entorhinal cortex (EC) is one of the earliest pathological hallmarks in patients with Alzheimer’s disease (AD). It can occur before significant Aβ deposition and appears to “spread” into anatomically connected brain regions. To determine whether this early-stage pathology is sufficient to cause disease progression and cognitive decline in experimental models, we overexpressed mutant human tau (hTauP301L) predominantly in layer II/III neurons of the mouse EC. Cognitive functions remained normal in mice at 4, 8, 12 and 16 months of age, despite early and extensive tau accumulation in the EC. Perforant path (PP) axon terminals within the dentate gyrus (DG) contained abnormal conformations of tau even in young EC-hTau mice, and phosphorylated tau increased with age in both the EC and PP. In old mice, ultrastructural alterations in presynaptic terminals were observed at PP-to-granule cell synapses. Phosphorylated tau was more abundant in presynaptic than postsynaptic elements. Human and pathological tau was also detected within hippocampal neurons of this mouse model. Thus, hTauP301L accumulation predominantly in the EC and related presynaptic pathology in hippocampal circuits was not sufficient to cause robust cognitive deficits within the age range analyzed here. 相似文献
5.
6.
Abstract— The amount of α-melanocyte-stimulating hormone (α-MSH) in the entire hypothalamus as well as the amount of α-MSH in free granule and synaptosome fractions of hypothalamic homogenates was investigated throughout the lifespan of female rats (1-24 months). A 900 g supernatant fluid was prepared from hypothalami following homogenization in an iso-osmotic sucrose solution, and free granules and synaptosomes containing α-MSH were fractionated by means of continuous sucrose density gradient centrifugation. α-MSH was quantified by radioimmunoassay. The total amount of α-MSH in the hypothalamus, as well as the amount in free granules and synaptosomes prepared from hypothalami increased progressively from the 1st to the 5th month of life, and this increase was more pronounced in the free granules than in the synaptosomes. On the other hand, the amount of α-MSH in the hypothalamus and the amount present in free granules and synaptosomes prepared from 5-24-month-old animals decreased with age, and this decrease appeared to proceed at similar rates in both subcellular compartments. Based on these results, it is suggested that ageing of α-MSH neurons in the hypothalamus is accompanied by a degeneration of the axons and/or an alteration in the biosynthetic and degradative activities of the neuron. 相似文献
7.
8.
Purification, characterization and immunolocalization of fimbrial protein from Porphyromonas (bacteroides) gingivalis. 总被引:3,自引:0,他引:3
H T Sojar J Y Lee G S Bedi M I Cho R J Genco 《Biochemical and biophysical research communications》1991,175(2):713-719
Rapid and reproducible method is described here for the purification of the 43 kDa fimbrial protein from P. gingivalis by preferential fractionation in the presence of 1% SDS and 0.2M of a bivalent cation at pH 6.5. Homogeneity of the purified 43 kDa was confirmed by SDS-PAGE and Western blot analysis using monoclonal and polyclonal antibodies raised against this protein. Amino acid composition and the amino acid sequence of the first 30 amino acid residues of the purified fimbriae are consistent with the composition and sequence predicted from the cloned gene of the fimbrial subunit. Circular dichroism spectra shows high levels of beta-sheet structure. The purified 43 kDa polymer shows fimbriae-like morphology under the electron microscope. Ultrastructural localization of the 43 kDa protein by the immunogold technique revealed specific labeling of the fimbriae with a diameter of approximately 3.5 to 5.0 nm. Localization of this protein suggest that the 43 kDa component is a fimbrial subunit. 相似文献
9.
Jeffrey P Mower Pascal Touzet Julie S Gummow Lynda F Delph Jeffrey D Palmer 《BMC evolutionary biology》2007,7(1):135
Background
It has long been known that rates of synonymous substitutions are unusually low in mitochondrial genes of flowering and other land plants. Although two dramatic exceptions to this pattern have recently been reported, it is unclear how often major increases in substitution rates occur during plant mitochondrial evolution and what the overall magnitude of substitution rate variation is across plants. 相似文献10.
Susan J. Harrison-Uy Julie A. Siegenthaler Andrea Faedo John L. R. Rubenstein Samuel J. Pleasure 《PloS one》2013,8(3)
We examined the role of the orphan nuclear hormone receptor CoupTFI in mediating cortical development downstream of meningeal retinoic acid signaling. CoupTFI is a regulator of cortical development known to collaborate with retinoic acid (RA) signaling in other systems. To examine the interaction of CoupTFI and cortical RA signaling we utilized Foxc1-mutant mice in which defects in meningeal development lead to alterations in cortical development due to a reduction of RA signaling. By analyzing CoupTFI−/−;Foxc1H/L double mutant mice we provide evidence that CoupTFI is required for RA rescue of the ventricular zone and the neurogenic phenotypes in Foxc1-mutants. We also found that overexpression of CoupTFI in Foxc1-mutants is sufficient to rescue the Foxc1-mutant cortical phenotype in part. These results suggest that CoupTFI collaborates with RA signaling to regulate both cortical ventricular zone progenitor cell behavior and cortical neurogenesis. 相似文献