全文获取类型
收费全文 | 1901篇 |
免费 | 147篇 |
专业分类
2048篇 |
出版年
2023年 | 17篇 |
2022年 | 23篇 |
2021年 | 45篇 |
2020年 | 27篇 |
2019年 | 41篇 |
2018年 | 51篇 |
2017年 | 42篇 |
2016年 | 68篇 |
2015年 | 91篇 |
2014年 | 99篇 |
2013年 | 137篇 |
2012年 | 153篇 |
2011年 | 139篇 |
2010年 | 98篇 |
2009年 | 80篇 |
2008年 | 112篇 |
2007年 | 97篇 |
2006年 | 107篇 |
2005年 | 95篇 |
2004年 | 80篇 |
2003年 | 87篇 |
2002年 | 75篇 |
2001年 | 21篇 |
2000年 | 15篇 |
1999年 | 21篇 |
1998年 | 27篇 |
1997年 | 14篇 |
1996年 | 13篇 |
1995年 | 15篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1992年 | 8篇 |
1991年 | 10篇 |
1990年 | 3篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 16篇 |
1983年 | 3篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1980年 | 6篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1976年 | 6篇 |
1974年 | 2篇 |
1971年 | 3篇 |
1970年 | 2篇 |
排序方式: 共有2048条查询结果,搜索用时 0 毫秒
1.
Riccardo E. Marioni Lars Penke Gail Davies Jennifer E. Huffman Caroline Hayward Ian J. Deary 《Proceedings. Biological sciences / The Royal Society》2014,281(1781)
Human cognitive ability shows consistent, positive associations with fitness components across the life-course. Underlying genetic variation should therefore be depleted by selection, which is not observed. Genetic variation in general cognitive ability (intelligence) could be maintained by a mutation–selection balance, with rare variants contributing to its genetic architecture. This study examines the association between the total number of rare stop-gain/loss, splice and missense exonic variants and cognitive ability in childhood and old age in the same individuals. Exome array data were obtained in the Lothian Birth Cohorts of 1921 and 1936 (combined N = 1596). General cognitive ability was assessed at age 11 years and in late life (79 and 70 years, respectively) and was modelled against the total number of stop-gain/loss, splice, and missense exonic variants, with minor allele frequency less than or equal to 0.01, using linear regression adjusted for age and sex. In both cohorts and in both the childhood and late-life models, there were no significant associations between rare variant burden in the exome and cognitive ability that survived correction for multiple testing. Contrary to our a priori hypothesis, we observed no evidence for an association between the total number of rare exonic variants and either childhood cognitive ability or late-life cognitive ability. 相似文献
2.
Y Nakashima N D Ferrante R L Jackson H J Pownall 《The Journal of biological chemistry》1975,250(14):5386-5392
Modifications of existing methods have allowed for the isolation and purification of various species of plasma glycosaminoglycans on the basis of their sulfate content and molecular size. All of the preparations precipitated human plasma low density lipoproteins (LDL); maximal precipitation occurred with amounts of glycans corresponding to 50 mug of hexuronate and 12 mg of LDL. The interaction of glycans with pyrene-labeled lipoproteins was also studied, measuring variations of the fluorescence emitted by the monomer (M) and excimer (E) species of the bound pyrene. The ratio IE/IM is proportional to c/eta, where c is the microscopic concentration of the pyrene confined to the hydrocarbon region of the lipoprotein and eta is the microviscosity of that region. To 0.12 mg of pyrene-labeled LDL, very low density lipoproteins (VLDL) or high density lipoproteins (HDL) were added increasing amounts of the various glycan preparations. The sulfate-rich species decreased the IE/IM ratio of LDL and HDL but not that of VLDL. This finding suggests that the glycan caused a change in lipoprotein conformation associated with either an increased volume or increased microscopic viscosity of the hydrocarbon region. The modification of LDL conformation could be prevented by proteolytic treatment of the sulfate-rich species or by addition to the system of suitable amounts of sulfate-poor species or of chrondroitin-4-sulfate, but could not be prevented by increased ionic concentration. These results suggest that the two main species of plasma glycans are important in maintaining adequate rheological properties of plasma lipoproteins. 相似文献
3.
Although a number of mechanisms have been put forward for immunity to malaria, their importance remains to be clarified. One of the important findings is that nonactivated monocytes and macrophages showed marked antiplasmodial activity in vitro. Recently we postulated that parasites may induce host factors that may depress the natural antiplasmodial activity of monocytes. In this investigation we identify IL-4 as a lymphokine that could function in this capacity. Human monocytes and macrophages in the absence of antiplasmodial antibody showed substantial killing of the asexual erythrocytic forms of Plasmodium falciparum as determined by a radiometric assay. Suppression of this killing was seen if the mononuclear phagocytes were pretreated with human rIL-4 at concentrations of 10 to 250 U with optimum activity between 100 and 250 U/2 x 10(5) cells. Cells from some individuals were rendered completely inactive by the IL-4 treatment. In contrast, IL-4 did not affect the neutrophil-mediated anti-P. falciparum activity. Our work identifies a potentially important parasite immune evasion mechanism involving IL-4 suppression of macrophage antiparasite activity. 相似文献
4.
Riccardo Montioli Carlotta Zamparelli Carla Borri Voltattorni Barbara Cellini 《The protein journal》2017,36(3):174-185
Human ornithine δ-aminotransferase (hOAT) (EC 2.6.1.13) is a mitochondrial pyridoxal 5′-phosphate (PLP)-dependent aminotransferase whose deficit is associated with gyrate atrophy, a rare autosomal recessive disorder causing progressive blindness and chorioretinal degeneration. Here, both the apo- and holo-form of recombinant hOAT were characterized by means of spectroscopic, kinetic, chromatographic and computational techniques. The results indicate that apo and holo-hOAT (a) show a similar tertiary structure, even if apo displays a more pronounced exposure of hydrophobic patches, (b) exhibit a tetrameric structure with a tetramer-dimer equilibrium dissociation constant about fivefold higher for the apoform with respect to the holoform, and (c) have apparent Tm values of 46 and 67?°C, respectively. Moreover, unlike holo-hOAT, apo-hOAT is prone to unfolding and aggregation under physiological conditions. We also identified Arg217 as an important hot-spot at the dimer–dimer interface of hOAT and demonstrated that the artificial dimeric variant R217A exhibits spectroscopic properties, Tm values and catalytic features similar to those of the tetrameric species. This finding indicates that the catalytic unit of hOAT is the dimer. However, under physiological conditions the apo-tetramer is slightly less prone to unfolding and aggregation than the apo-dimer. The possible implications of the data for the intracellular stability and regulation of hOAT are discussed. 相似文献
5.
Intrinsic processes are assumed to underlie life history expression and trade‐offs, but extrinsic inputs are theorised to shift trait expression and mask trade‐offs within species. Here, we explore application of this theory across species. We do this based on parentally induced embryo temperature as an extrinsic input, and mass‐specific embryo metabolism as an intrinsic process, underlying embryonic development rate. We found that embryonic metabolism followed intrinsic allometry rules among 49 songbird species from temperate and tropical sites. Extrinsic inputs via parentally induced temperatures explained the majority of variation in development rates and masked a relationship with metabolism; metabolism explained a minor proportion of the variation in development rates among species, and only after accounting for temperature effects. We discuss evidence that temperature further obscures the expected interspecific trade‐off between development rate and offspring quality. These results demonstrate the importance of considering extrinsic inputs to trait expression and trade‐offs across species. 相似文献
6.
F Amenta C Cavallotti W L Collier F Ferrante P Geppetti A Ricci 《Regulatory peptides》1989,26(1):9-17
By the use of combined in vitro radioreceptor binding and autoradiographic techniques, we analyzed the pharmacological properties and the anatomical localization of the vasoactive intestinal polypeptide (VIP) receptor in rat superior mesenteric artery and in medium and small mesenteric artery branches. 125I-VIP was bound by sections of rat superior mesenteric artery in a manner consistent with the labeling of specific VIP receptors, with Kd and Bmax values of 0.23 nM and 0.71 pmol/mg protein respectively. Inhibition of 125I-VIP binding with VIP and related peptides gives the following rank order of potency: VIP greater than peptide histidine methionine greater than secretin. Light microscope autoradiography reveals specific VIP binding sites within the medial layer of superior mesenteric artery and its branches. Medium and small sized vessels are richer in 125I-VIP binding sites than the larger ones. 相似文献
7.
In flow cytometric measurement of cell DNA distribution one of the major problems is accounting for the effect of fragmentation
in the staining process. This work considers a recent probabilistic model that has been proposed for the fragmentation process
and species under which conditions it is possible to uniquely identify the DNA distributions of the original population using
flow cytometric data. Attention is given both to the normal and to the polyploid case.
This work was partially supported by a grant of the Italian National Research Council, Special Project “Oncology”, contract
number 84.00632.44. 相似文献
8.
Marina Pitto Anna Miglio Gunther Kirschner Alberta Leon Riccardo Ghidoni 《Neurochemical research》1991,16(11):1187-1192
Semisynthetic single-chain GM1 derivatives containing N-acetyl-sphingosine (LIGA4) or N-dichloroacetyl-sphingosine (LIGA20) were recently reported to exert strong protection against glutamate-induced neuronal death in primary cultures of cerebellar granule cells. Elucidation of the molecular mechanism underlying the evoked effect requires knowledge of the metabolic fate of such molecules in the same cultured cells. For this, LIGA4 and LIGA20 were made radioactive on the long chain base moiety and added to cerebellar granule cells in culture in parallel with GM1 ganglioside. The metabolic fate was then investigated. It was found that both these molecules were easily taken up by the cells and promptly metabolized in a fashion qualitatively similar to that of control GM1. The highest amount processed was attributed to the different aggregation properties of LIGAs in solution. Among metabolites, higher accumulation of the single-chain ceramide residues was found after LIGA administration. Interestingly, sphingomyelin was generated, regardless the added compound, suggesting a recycling of the free long chain base. 相似文献
9.
Fragments of ascidian eggs, but at random in any plane and ranging in size from 10 to 90% of the total egg volume, displayed the electrical characteristics of the intact egg, having a resting potential of -86 mV and giving rise to an action potential upon stimulation by electrical current injection. Following insemination, the fragments generated fertilization potentials, comparable to those of intact eggs, although the repolarization phase was shorter. Our data show that there are sufficient ion channels throughout the egg surface to generate action potentials and fertilization potentials in excised egg fragments, irrespective of their global origin. Furthermore, the fertilizing spermatozoon is capable of activating fertilization channels in areas of the egg plasma membrane not destined for sperm entry. 相似文献
10.
Christina Brahe Isabella Velonà Gerrit van der Steege Stefania Zappata Anneke Y. van de Veen Jan Osinga Carli M. J. Tops Riccardo Fodde P. Meera Khan Charles H. C. M. Buys Giovanni Neri 《Human genetics》1994,93(5):494-501
The locus responsible for the childhood-onset proximal spinal muscular atrophies (SMA) has recently been mapped to an area of 2–3 Mb in the region q12–13.3 of chromosome 5. We have used a series of radiation hybrids (RHs) containing distinct parts of the SMA region as defined by reference markers. A cosmid library was constructed from one RH. Thirteen clones were isolated and five of these were mapped within the SMA region. Both RH mapping and fluorescence in situ hybridization analysis showed that two clones map in the region between loci D5S125 and D5S351. One of the cosmids contains expressed sequences. Polymorphic dinucleotide repeats were identified in both clones and used for segregation analysis of key recombinant SMA families. One recombination between the SMA locus and the new marker 9Ic (D5S685) indicates that 9Ic is probably the closest distal marker. The absence of recombination between the SMA locus and marker Fc (D5S684) suggests that Fc is located close to the disease gene. These new loci should refine linkage analysis in SMA family studies and may facilitate the isolation of the disease gene. 相似文献