全文获取类型
收费全文 | 557篇 |
免费 | 38篇 |
出版年
2023年 | 2篇 |
2022年 | 6篇 |
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 10篇 |
2018年 | 14篇 |
2017年 | 18篇 |
2016年 | 12篇 |
2015年 | 34篇 |
2014年 | 33篇 |
2013年 | 43篇 |
2012年 | 43篇 |
2011年 | 44篇 |
2010年 | 30篇 |
2009年 | 17篇 |
2008年 | 19篇 |
2007年 | 23篇 |
2006年 | 26篇 |
2005年 | 31篇 |
2004年 | 16篇 |
2003年 | 27篇 |
2002年 | 15篇 |
2001年 | 7篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1962年 | 1篇 |
1960年 | 3篇 |
1959年 | 2篇 |
1949年 | 1篇 |
1915年 | 1篇 |
1914年 | 2篇 |
排序方式: 共有595条查询结果,搜索用时 15 毫秒
1.
Vasant Chellappa Kendra N. Taylor Kathryn Pedrick Carlos Donado Ilka Arun Netravali Khaleda Haider Annaiah Cariappa Natasha F. Dalomba Shiv Pillai 《PloS one》2013,8(1)
Catalytically defective rare variants of Sialic acid Acetyl Esterase (SIAE) have previously been linked to autoimmunity. Studies presented here confirm that the M89V SIAE protein and all other products of common variant alleles of SIAE are catalytically normal. Although overexpressing transfected non-lymphoid cells secrete small amounts of SIAE that can associate with the cell surface, normal human lymphocytes do not exhibit cell surface SIAE, supporting genetic evidence in mice that indicates that this protein functions in a lymphocyte intrinsic manner. Analyses of the plasma proteome also indicate that SIAE is not secreted in vivo. A re-analysis exclusively of catalytically defective rare variant alleles of SIAE in subjects in which this gene was completely sequenced confirmed an association of SIAE with autoimmunity. A subset of catalytically defective rare variant SIAE alleles has previously been typed in a large genotyping study comparing a diverse group of disease subjects and controls; our re-analysis of this data shows that catalytically defective alleles are enriched in disease subjects. These data suggest that SIAE may be associated with autoimmunity and that further study of catalytically defective rare variant SIAE alleles in terms of autoimmune disease susceptibility is strongly warranted. 相似文献
2.
Latika P. Chanderkar Gouri Shanker Robert L. Knobler Fred D. Lublin Woon Ki Paik Sangduk Kim 《Neurochemical research》1987,12(5):445-449
Mice with the dysmyelinating mutation shiverer were studied by measuring the activity of two protein methylases and myelin marker enzymes in the brain. It was observed thatS-adenosylmethionine: protein-lysineN-methyltransferase (protein methylase III, EC. 2.1.1.43) activity is significantly reduced in phenotypically affected homozygous shiverer (shi/shi) mutant mouse brain compared to the unaffected heterozygous littermate brain. This reduction in enzyme activity is manifested mainly by reduced formation of trimethyllysine during the in vitro methylation of histone. In contrast, myelin marker enzymes such as 2,3-cyclic nucleotide 3-phosphohydrolase and 5-nucleotidase as well asS-adenosyl-methionine: protein-carboxylO-methyltransferase (protein methylase II, EC. 2.1.1.24) activities were not significantly affected in these strains of mice. 相似文献
3.
The presence and specificity of insulin receptors was investigated in cultured cells obtained from 15–16 days old embryonic mouse cerebra. Developmental studies suggested that the maximum insulin binding occurred at about 11 days in vitro (DIV). Scatchard analysis of binding data revealed two types of binding sites. One type of receptor was the high affinity type (K
d=7.77×10–9 M; number of receptor sites,B
max=350 fmol/mg protein) while the other type was of low affinity type (K
d=5.75×10–8 M;B
max=1150 fmol/mg protein). The specificity of receptors for insulin was also confirmed by showing that [125I]insulin was displaced by non-radioactive insulin but not by glucagon or growth hormone. Insulin displayed a clear dose-dependent stimulation of thymidine incorporation. It also stimulated the activity of the enzyme 2,3-cyclic nucleotide phosphohydrolase (CNPase), which is specifically associated with myelin produced from oligodendroglia. Thus insulin has a positive influence on the proliferation and differentiation of brain cells. 相似文献
4.
Recently attempts have been made to establish the presence and to determine the metabolic versatility of microorganisms in
the terrestrial deep subsurface at the Savannah River Plant, Aiken, SC, USA. Sediment samples obtained at 20 different depths
of up to 526 m were examined to determine carbon mineralization under aerobic, sulfate-reducing, and methanogenic conditions.
The evolution of14CO2 from radiolabelled glucose was observed under aerobic conditions in all sediments, whereas pyridine was transformed in 50%
of the 20 sediments and indole was metabolized in 85% of the sediments. Glucose mineralization in certain sediments was comparable
to that in the surface environment. Sulfate was reduced in only five sediments, and two were carbon limited. Methane production
was detected in ten sediments amended with formate only after long-term incubations. The transformation of indole and pyridine
was only rarely observed under sulfate-reducing conditions and was never detected in methanogenic incubations. This study
provides information concerning the metabolic capability of both aerobic and anaerobic microorganisms in the deep subsurface
and may prove useful in determining the feasibility of microbial decontamination of such environments. 相似文献
5.
The pathogenesis of neuronal dysfunction in the gangliosidoses is poorly understood. Studies of the feline gangliosidoses and in vitro experiments implicate ganglioside inhibition of protein kinase C (PKC) in the pathogenesis of these neurological diseases. Therefore, in the present study, the binding of [3H]phorbol-12, 13 dibutyrate was measured to determine the levels of PKC in cerebral cortex of cats with GM1 gangliosidosis (mutant) and age matched normal siblings. This binding of ([3H]PDB) to cerebral cortex homogenates in both normal and mutant cats was highly specific. The specificity of receptors was ascertained also from displacement studies using nonradioactive phorbol ester analogues to displace [3H]PDB bound to its receptors. In both mutant and normal cat brain, phorbol 12, 13-dibutyrate (PDB), 4--phorbol 12,13-didecanoate (-PDA) and 4--phorbol 12,13-dibenzoate (-PDBz) were highly potent (approximately to same degree) and effective in displacing [3H]PDB. On the other hand, 4- phorbol 12,13-diacetate (-PDA) was a weak displacer and 4--phorbol did not displace the bound [3H]PDB in either normal or mutant brain. Scatchard analysis of the binding data indicated a homogenous single class of binding sites in normal and mutant brain (Normal: Kd=1.42×10–7 M, Bmax=8.40 pmoles/mg protein. Mutant: Kd=1.60×10–7 M, Bmax=10.00 pmoles/mg protein). Sphingosine inhibited the binding to approximately the same extent in normal and mutant cortex. These studies demonstrate the presence of highly specific, homogenous, single type phorbol ester receptors in cerebral cortex of cats with GM1 gangliosidosis which are qualitatively and quantitatively similar to normal cat brain. 相似文献
6.
In a study of the kinetics of 5-hydroxytryptamine (5-HT) in platelets in 26 hypertensive subjects with a mean systolic and diastolic blood pressure of 153.9 +/- 26.9 and 106.9 +/- 9.1 mm Hg respectively, it has been observed that in hypertensive platelets there was a marked decrease in 5-HT uptake and content, an increase in 5-HT efflux and an accompanying increase in Plasma 5-HT and 5-HIAA levels. Regression analysis of the data indicated a significant correlation between rise in diastolic blood pressure and these changes in 5-HT kinetics. 相似文献
7.
Marco A. Marra Shiv S. Prasad David L. Baillie 《Molecular & general genetics : MGG》1993,236(2-3):289-298
Summary A previous study of genomic organization described the identification of nine potential coding regions in 150 kb of genomic DNA from the unc-22(IV) region of Caenorhabditis elegans. In this study, we focus on the genomic organization of a small interval of 0.1 map unit bordered on the right by unc-22 and on the left by the left-hand breakpoints of the deficiencies sDf9, sDf19 and sDf65. This small interval at present contains a single mutagenically defined locus, the essential gene let-56. The cosmid C11F2 has previously been used to rescue let-56. Therefore, at least some of C11F2 must reside in the interval. In this paper, we report the characterization of two coding elements that reside on C11F2. Analysis of nucleotide sequence data obtained from cDNAs and cosmid subclones revealed that one of the coding elements closely resembles aromatic amino acid decarboxylases from several species. The other of these coding elements was found to closely resemble a human growth factor activatable Na+/H+ antiporter. Pairs of oligonucleotide primers, predicted from both coding elements, have been used in PCR experiments to position these coding elements between the left breakpoint of sDf19 and the left breakpoint of sDf65, between the essential genes let-653 and let-56. 相似文献
8.
9.
10.
R Shanker R K Dogra S Khanna S N Srivastava L J Shukla S Gupta J C Katiyar 《Indian journal of experimental biology》1992,30(5):388-393
Pathomorphological and immunological studies were carried out on rodents following oral administration of 0, 0.1, 0.25 and 0.5% (w/w) metanil yellow, mixed in diet, for 30 days. No significant change in hematologic parameters and histologic architecture of liver, kidney, mesenteric lymph node, thymus and urinary bladder was observed except for mild desquamation of intestinal villi and moderate changes in Peyer's patches of small intestine with higher doses. Among immunological parameters, significant enhancement in the primary humoral immune response (anti-SRBC IgM plaque forming cells of spleen) was observed with the lowest dose of metanil yellow while higher doses produced opposing effects. An elevated cutaneous delayed type hypersensitivity (DTH) reaction to SRBC was seen in 0.1% metanil yellow treated animals but higher doses did not influence the reaction. The treatment also caused changes in functional capabilities of macrophages. Although these immune alterations could hardly influence the local immunity of gut, as measured by the capacity of animals to cause rejection of Nippostrongylus brasiliensis parasite, the potential to modulate the immunity in general by metanil yellow however assumes considerable biological significance. 相似文献