全文获取类型
收费全文 | 2445篇 |
免费 | 137篇 |
国内免费 | 3篇 |
出版年
2023年 | 5篇 |
2022年 | 15篇 |
2021年 | 26篇 |
2020年 | 13篇 |
2019年 | 22篇 |
2018年 | 30篇 |
2017年 | 25篇 |
2016年 | 44篇 |
2015年 | 49篇 |
2014年 | 86篇 |
2013年 | 103篇 |
2012年 | 140篇 |
2011年 | 155篇 |
2010年 | 77篇 |
2009年 | 103篇 |
2008年 | 151篇 |
2007年 | 162篇 |
2006年 | 144篇 |
2005年 | 149篇 |
2004年 | 143篇 |
2003年 | 139篇 |
2002年 | 127篇 |
2001年 | 63篇 |
2000年 | 57篇 |
1999年 | 59篇 |
1998年 | 36篇 |
1997年 | 33篇 |
1996年 | 23篇 |
1995年 | 29篇 |
1994年 | 26篇 |
1993年 | 15篇 |
1992年 | 35篇 |
1991年 | 37篇 |
1990年 | 19篇 |
1989年 | 23篇 |
1988年 | 17篇 |
1987年 | 20篇 |
1986年 | 17篇 |
1985年 | 25篇 |
1984年 | 16篇 |
1983年 | 19篇 |
1982年 | 7篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 14篇 |
1978年 | 8篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1973年 | 5篇 |
1933年 | 4篇 |
排序方式: 共有2585条查询结果,搜索用时 15 毫秒
1.
Selective diapedesis of Th1 cells induced by endothelial cell RANTES. 总被引:16,自引:0,他引:16
T Kawai M Seki K Hiromatsu J W Eastcott G F Watts M Sugai D J Smith S A Porcelli M A Taubman 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(6):3269-3278
Differentiated CD4 T cells can be divided into Th1 and Th2 types based on the cytokines they produce. Differential expression of chemokine receptors on either the Th1-type or the Th2-type cell suggests that Th1-type and Th2-type cells differ not only in cytokine production but also in their migratory capacity. Stimulation of endothelial cells with IFN-gamma selectively enhanced transmigration of Th1-type cells, but not Th2-type cells, in a transendothelial migration assay. Enhanced transmigration of Th1-type cells was dependent on the chemokine RANTES produced by endothelial cells, as indicated by the findings that Ab neutralizing RANTES, or Ab to its receptor CCR5, inhibited transmigration. Neutralizing Ab to chemokines macrophage-inflammatory protein-1alpha or monocyte chemotactic protein-1 did not inhibit Th1 selective migration. Whereas anti-CD18 and anti-CD54 blocked basal levels of Th1-type cell adherence to endothelial cells and also inhibited transmigration, anti-RANTES blocked only transmigration, indicating that RANTES appeared to induce transmigration of adherent T cells. RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor. Thus, enhancement of Th1-type selective migration appeared to be responsible for the diapedesis induced by interaction between CCR5 on Th1-type cells and RANTES produced by endothelial cells. Further evidence that CCR5 and RANTES play a modulatory role in Th1-type selective migration derives from the abrogation of this migration by anti-RANTES and anti-CCR5 Abs. 相似文献
2.
Y Ishikawa K Kobayashi K Seki H Mizutani Y Kawasaki J Koike K Ijiri M Yamashita K Sugiura J Poynter T MacCallum G Anderson 《Biological Sciences in Space》1998,12(4):366-372
Several soluble components, peptidase and amino acids, and carbon isotopic ratio in the water retrieved from flight experiments of Autonomous Biological Systems (ABS) as well as ground control samples are analyzed to interpret the condition, dynamics, material balance of the ABS ecosystems. Organic carbons in flight samples were found to be more abundant compared with the control ones, which suggested the uniform ecosystems in low gravity might easily dissolve more soluble components. The Mir-1997 flight sample showed higher C/N ratio probably because of the dissolution of carbon-rich plant materials. 相似文献
3.
NatB is an N-terminal acetyltransferase consisting of a catalytic Nat5 subunit and an auxiliary Mdm20 subunit. In yeast, NatB acetylates N-terminal methionines of proteins during de novo protein synthesis and also regulates actin remodeling through N-terminal acetylation of tropomyosin (Trpm), which stabilizes the actin cytoskeleton by interacting with actin. However, in mammalian cells, the biological functions of the Mdm20 and Nat5 subunits are not well understood. In the present study, we show for the first time that Mdm20-knockdown (KD), but not Nat5-KD, in HEK293 and HeLa cells suppresses not only cell growth, but also cellular motility. Although stress fibers were formed in Mdm20-KD cells, and not in control or Nat5-KD cells, the localization of Trpm did not coincide with the formation of stress fibers in Mdm20-KD cells. Notably, knockdown of Mdm20 reduced the expression of Rictor, an mTORC2 complex component, through post-translational regulation. Additionally, PKCαS657 phosphorylation, which regulates the organization of the actin cytoskeleton, was also reduced in Mdm20-KD cells. Our data also suggest that FoxO1 phosphorylation is regulated by the Mdm20-mTORC2-Akt pathway in response to serum starvation and insulin stimulation. Taken together, the present findings suggest that Mdm20 acts as a novel regulator of Rictor, thereby controlling mTORC2 activity, and leading to the activation of PKCαS657 and FoxO1. 相似文献
4.
Ono Mayumi Kuwano Michihiko Mizushima Shoji 《Molecular genetics and genomics : MGG》1979,170(1):11-23
Molecular Genetics and Genomics - Ribosomal protein S1 from a newly isolated Escherichia coli mutant has a molecular weight of about 54,000 which is smaller than the wild type S1 (M.W. 65,000). The... 相似文献
5.
K Sakurai N Seki R Fujii K Yagui Y Tokuyama F Shimada H Makino Y Suzuki N Hashimoto Y Saito T Egashira K Matsui A Kanatsuka 《Hormones et métabolisme》2000,32(8):316-320
Mutations of the hepatocyte nuclear factor 4 alpha (HNF-4alpha) gene have been demonstrated in maturity-onset diabetes of the young (MODY) 1 families. To investigate the possibility that the HNF-4alpha gene contributes to the onset of non-insulin-dependent diabetes mellitus (NIDDM) in Japanese patients, we screened all exons and flanking introns of this gene for mutations in 100 patients with NIDDM diagnosed after 25 years of age. We identified two missense mutations: M49V in exon 1c and T1301 in exon 4; and two nucleotide substitutions in introns: cytosine to thymidine at -5 nt in intron 1b and adenine to thymidine at -21 nt in intron 5. We screened an additional 220 diabetic subjects for the polymorphism in intron 1b. The c/t substitution in intron 1b was associated with NIDDM. This substitution in the polypyrimidine tract, an important cis-acting element directing intron removal, is likely to influence pre-mRNA splicing of this gene. T1301 in exon 4 was observed in only two diabetic subjects. This mutation could influence the conformation of this peptide, resulting in changes in ligand binding domain function. M49V in exon 1c was found in both diabetic and non-diabetic subjects; isoforms HNF-4alpha 4, 5, and 6 with this mutation may impair glucose metabolism in tissue. In contrast to the primary cause of nonsense and missense mutations of the HNF-4alpha gene in MODY1, the nucleotide substitution in intron 1b may partially contribute to development of NIDDM in combination with other genetic and environmental factors. 相似文献
6.
Abstract: Prostaglandin H-E isomerase (EC 5.3.99.3) was purified from human brain cytosol. Purification was by ammonium sulfate fractionation, diethylaminoethyl-Sephar-ose chromatography, gel filtration on a BioGel P-100 column, GSH-agarose chromatography, and MonoQ chromatography. The activity was eluted in two peaks from the MonoQ column, which were designated peaks 1 and 2. The molecular weights of peaks 1 and 2, determined by gel filtration, were 42,000 and 44,000, respectively. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, peak 1 showed two bands at the molecular weights of 24,500 and 25,000, and peak 2 showed a single band at the molecular weight of 25,000, results suggesting that both were dimeric proteins. The pI values of both enzymes were ∼5.4. The enzymes catalyzed selective conversion of prostaglandin H2 to prostaglandin E2 . The K m values for prostaglandin H2 of peaks 1 and 2 were 147 and 308 μ M , respectively, and the V max values were 380 and 720 nmol/min/mg of protein, respectively. GSH was required for the catalysis of both enzymes, and no other sulfhydryl compounds could support the reaction. A part of glutathione S -transferase (EC 2.5.1.18) was copurified with peaks 1 and 2 of prostaglandin H-E isomerase. Prostaglandin H-E isomerase activity of peak 2 enzyme was competitively inhibited by 1-chloro-2,4-dinitrobenzene, a substrate of glutathione S -transferase. These results suggested that prostaglandin H-E isomerases in human brain cytosol were identical with anionic forms of glutathione S -transferase. 相似文献
7.
To investigate how various concentrations of serum prolactin (PRL) influence the priming effect of luteinizing hormone releasing hormone (LH-RH) on the pituitary gland, 24 women with various blood PRL concentrations received intravenous injections of 100 micrograms of synthetic LH-RH twice at an interval of 60 minutes and their serum LH and follicle-stimulating hormone (FSH) were measured and analysed. In the follicular phase with a normal PRL concentration (PRL less than 20 ng/ml, n = 6), marked first peaks of the two hormones following the first LH-RH stimulation and enhanced second peaks after the second LH-RH administration were observed, indicating a typical priming effect of LH-RH on gonadotropins, though the second response of FSH was more moderate than that of LH. In hyperprolactinemia, in which the serum PRL concentration was higher than 70 ng/ml (n = 13), the basal concentration of gonadotropins was not significantly changed but the priming effect of LH-RH on LH and FSH was significantly decreased (p less than 0.01). No marked second peaks of LH and FSH were observed, suggesting an inhibitory effect of hyperprolactinemia on the second release of LH and FSH. In contrast, this effect was restored in a group of women whose serum PRL concentration was between 30 and 50 ng/ml (n = 5). Furthermore, enhanced second peaks of both LH and FSH were noted after successful bromocriptine therapy reduced hyperprolactinemia (PRL greater than 70 ng/ml) to less than 25 ng/ml (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
Tetsunori Seki 《Immunogenetics》1989,30(1):5-12
Two varieties of similar, but structurally distinct, cDNA clones for the human low-affinity receptors for the Fc portion of
immunoglobulin G (FcγRII) have been isolated. One type of clone was obtained from human B lymphocytes, and the other from
PHA-activated peripheral T cells and monocytes. Transfection of both prototype clones into Cos-7 cells and subsequent specific
staining with monoclonal antibodies of the CDw32 group confirmed the identification of the gene products. The nucleotide sequence
of the cDNA clone from B lymphocytes contains an open reading frame that encodes a protein of relative mass (M
r) 27000 with an extracellular domain of 179 amino acids containing three potential N-glycosylation sites, a 26 amino acid
transmembrane domain, and a 44 amino acid cytoplasmic domain. The clones from peripheral T cells and monocytes both encoded
a protein ofM
r 31000 with a 179 amino acid extracellular domain containing two potential N-glycosylation sites and a 26 amino acid transmembrane
domain. The two types of clones had similar sequences in their immunoglobulin-like extracellular and transmembrane domains,
but differed in their leader sequences and 3′-untranslated regions. The most notable difference between the clones was the
presence of a distinctive 76 amino acid cytoplasmic domain in those isolated from T cells and monocytes. 相似文献
9.
10.
Shin-Ichi Hayama Rika Akamatsu Mayumi Kishimoto Masatsugu Suzuki Hideo Nigi 《Primates; journal of primatology》1988,29(3):423-426
Diverticular disease of the colon was detected in a female Japanese monkey by X-ray examination. The monkey was 15 years old
and had been kept under captive conditions for nine years. Lack of appetite and activity, and constipation were observed.
The monkey was given fiber-rich vegetables and wild plants, and its appetite and activity then improved. Based on a consideration
of various factors, it is suggested that one possible cause of the diverticulosis in this case was a low dietary fiber intake. 相似文献