全文获取类型
收费全文 | 1587篇 |
免费 | 94篇 |
专业分类
1681篇 |
出版年
2024年 | 5篇 |
2023年 | 6篇 |
2022年 | 18篇 |
2021年 | 22篇 |
2020年 | 19篇 |
2019年 | 32篇 |
2018年 | 28篇 |
2017年 | 41篇 |
2016年 | 53篇 |
2015年 | 64篇 |
2014年 | 66篇 |
2013年 | 90篇 |
2012年 | 119篇 |
2011年 | 123篇 |
2010年 | 74篇 |
2009年 | 52篇 |
2008年 | 108篇 |
2007年 | 88篇 |
2006年 | 83篇 |
2005年 | 74篇 |
2004年 | 87篇 |
2003年 | 73篇 |
2002年 | 63篇 |
2001年 | 23篇 |
2000年 | 23篇 |
1999年 | 18篇 |
1998年 | 12篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1992年 | 29篇 |
1991年 | 19篇 |
1990年 | 13篇 |
1989年 | 7篇 |
1988年 | 10篇 |
1987年 | 8篇 |
1986年 | 12篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 9篇 |
1981年 | 5篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1977年 | 7篇 |
1975年 | 5篇 |
1974年 | 8篇 |
1971年 | 4篇 |
1970年 | 5篇 |
1968年 | 6篇 |
1967年 | 4篇 |
排序方式: 共有1681条查询结果,搜索用时 15 毫秒
101.
The survival rate of male Fischer-344/Du rats treated chronically with high doses of deprenyl was investigated. Eighteen month old rats were treated with 1 mg/kg s.c. deprenyl 3 times per week for 13 months. At the age of 31 months, treated rats showed a greater mortality rate with three of 12 rats surviving, while in saline-treated control animals seven of 12 animals survived. No significant differences in superoxide dismutase (SOD) or catalase (CAT) activities in brain regions of control and treated animals were seen at 31 months of age. In contrast, when 27 month old rats were treated in the same manner for one month, significant increases in SOD (both Cu,Zn- and Mn-) and CAT activities were found in substantia nigra, striatum and cerebral cortex, but not in hippocampus. This effect was produced with a wide range of deprenyl doses (0.25-2 mg/kg, but not 4 mg/kg). Although a causal relationship between the two different effects of the drug, i.e. 1) increases in antioxidant enzyme activities and 2) the prolongation of survival of animals, has not been directly demonstrated, the loss of both effects with the high dose of the drug in the present experiment may be taken as circumstantial evidence for their causal relationship. 相似文献
102.
One of the photosystem II reaction center proteins, D1, is encoded by the psbA gene and is synthesized as a precursor form with a carboxyl-terminal extension that is subsequently cleaved between Ala-344 and Ser-345. We have generated three psbA transformants of the green alga Chlamydomonas reinhardtii in which Ala-344 or Ser-345 have been substituted with Pro or Glu (A344P, S345E, and S345P) to understand the effects of the amino acid substitutions on the processing of the precursor D1. S345E grew photoautotrophically and showed PSII activity like the wild type. However, A344P and S345P were unable to grow photoautotrophically and were significantly photosensitive. A344P was deficient in the processing of precursor D1 and in oxygen-evolving activity, but assembled photosystem II complex capable of charge separation. In contrast, both precursor and mature forms of D1 accumulated in S345P cells from the logarithmic phase and the cells evolved oxygen at 18% of wild-type level. However, S345P cells from the stationary phase contained mostly the mature D1 and showed a twofold increase in oxygen-evolving activity. The rate of processing of the accumulated pD1 was estimated to be about 100 times slower than in the wild type. It is therefore concluded that the functional oxygen-evolving complex is assembled when the precursor D1 is processed, albeit at a very low rate. These results suggest the functional significance of the amino acid residues at the processing site of the precursor D1. 相似文献
103.
J. Barry III Whitney Aya Leder Jada Lewis Raymond A. Popp Chris Paszty Edward M. Rubin W. Ronald Shehee Tim M. Townes Oliver Smithies 《Biochemical genetics》1998,36(1-2):65-77
The hematology of the laboratory mouse has beenwell characterized. Normal genetic differences at thealpha- and beta-globin gene loci serve as useful markersfor a wide variety of types of experimental studies. There are a number of naturallyoccurring or induced mutations that disrupt globinexpression and produce thalassemic phenotypes. Inaddition, much has been learned of the workings of theglobin locus control region from studies of transgenicmice, including those with mutations induced by targetedsite-specific modifications. After a new mutation ortransgene has been created, it must be maintained in living mice, and the genotypes of theoffspring must be ascertained. While it is possible todetermine genotypes by DNA analyses, such assays aretime consuming and relatively expensive. An osmoticchallenge test -- originally developed for thegenotyping of large-deletion alpha-thalassemia mutationsin mice -- has proven useful in detecting bothsevere and milder alpha- and beta-thalassemias, as wellas some transgenic genotypes in mice carrying human globin genes.Reliable genotyping can, in some cases, be completedwithin a few minutes with minimal expense.Quantification of red cell fragility for a variety ofthalassemic and transgenic mice is described here, alongwith a simplified test suitable for rapid, routinegenotyping. The osmotic challenge test is perfectlyreliable for distinguishing genotypes that causesignificantly decreased release of hemoglobin from the redcells, but it is also useful for some of the conditionsin which overall erythrocyte osmotic fragility isessentially normal. 相似文献
104.
Miyake M Sugano K Kawashima K Ichikawa H Hirabayashi K Kodama T Fujimoto H Kakizoe T Kanai Y Fujimoto K Hirao Y 《Biochemical and biophysical research communications》2007,362(4):865-871
Somatic mutations of the fibroblast growth factor receptor 3 (FGFR3) gene were detected by peptide nucleic acid (PNA)-mediated real-time PCR clamping. Mutation was detected in negative control containing only wild-type DNA due to a misincorporation of dNTPs to PNA binding sites when the amount of template DNA was decreased to 1 ng. Thus, the amount of template DNA was critical determinant of the assay sensitivity in PNA-mediated PCR clamping. Assay conditions were optimized to detect FGFR3 mutations in exons 7, 10, and 15, at a concentration of more than 1% mutated DNA using 50 ng of genomic DNA as the template. Mutations were detected in 12 of 13 (92.3%) tumor tissues and 11 of 13 (84.6%) urine samples from patients with superficial bladder cancer, while no mutations were detected in tissues and/or urine samples from patients with muscle-invasive bladder cancer or chronic cystitis. 相似文献
105.
Yoshiro Naito Hisashi Sawada Makiko Oboshi Aya Fujii Shinichi Hirotani Toshihiro Iwasaku Yoshitaka Okuhara Akiyo Eguchi Daisuke Morisawa Mitsumasa Ohyanagi Takeshi Tsujino Tohru Masuyama 《PloS one》2013,8(10)
Although iron is reported to be associated with the pathogenesis of chronic kidney disease, it is unknown whether iron participates in the pathophysiology of nephrosclerosis. Here, we investigate whether iron is involved in the development of hypertensive nephropathy and the effects of iron restriction on nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a high-salt diet developed severe hypertension and nephrosclerosis. As a result, survival rate was decreased after 8 weeks diet. Importantly, massive iron accumulation and increased iron content were observed in the kidneys of salt-loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2′-deoxyguanosine excretion, and urinary iron excretion; however, these changes were markedly attenuated by iron restriction. Of interest, expression of cellular iron transport proteins, transferrin receptor 1 and divalent metal transporter 1, was increased in the tubules of salt-loaded SHRSP. Notably, iron restriction attenuated the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP. Taken together, these results suggest a novel mechanism by which iron plays a role in the development of hypertensive nephropathy and establish the effects of iron restriction on salt-induced nephrosclerosis. 相似文献
106.
Cell surface glycans and recognition molecules of these glycans play important roles in cellular recognition and trafficking, such as in the inflammation response by sialyl LewisX oligosaccharides. Malignant cells also utilize a similar mechanism during colonization and establishment of tumor tissues in the host. These considerations prompt us to develop a screening method for comprehensive analysis of N-glycans derived from membrane fractions of cancer cells. The method involves two step separations. Initially, N-glycans released from cell membrane fractions with N-glycoamidase F were labeled with 2-aminobenzoic acid and separated based on the number of sialic acid residues attached to the oligosaccharides using affinity chromatography on a serotonin-immobilized stationary phase. Each of the nonretarded fractions containing asialo- and high-mannose type oligosaccharides and mono-, di-, tri-, and tetra-sialooligosaccharide fractions which were desialylated with neuraminidase was analyzed by a combination of HPLC using an Amide-80 column as the stationary phase and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We analyzed total N-glycan pools of membrane fractions obtained from some cancer cells, and found that U937 cells (Histocytic lymphoma cells) expressed a large amount of oligosaccharides having polylactosamine residues and MKN45 cells (Gastric adenocarcinoma cells) contained hyper-fucosylated oligosaccharides which contained multiple fucose residues. The method described here will be a powerful technique for glycomics studies in cell surface glycoproteins, and will enable one to search marker oligosaccharides characteristically observed in various diseases such as cancer, inflammation, and congenital disorder. 相似文献
107.
Satoru Kanai Hiroyuki Toh Toshiya Hayano Masakazu Kikuchi 《Journal of molecular evolution》1998,47(2):200-210
Protein disulfide isomerase (PDI) is an enzyme that promotes protein folding by catalyzing disulfide bridge isomerization.
PDI and its relatives form a diverse protein family whose members are characterized by thioredoxin-like (TX) domains in the
primary structures. The family was classified into four classes by the number and the relative positions of the TX domains.
To investigate the evolution of the domain structures, we aligned the amino acid sequences of the TX domains, and the molecular
phylogeny was examined by the NJ and ML methods. We found that all of the current members of the PDI family have evolved from
an ancestral enzyme, which has two TX domains in the primary structure. The diverse domain structures of the members have
been generated through domain duplications and deletions. 相似文献
108.
We studied the LET and ion species dependence of the RBE for cell killing to clarify the differences in the biological effects caused by the differences in the track structure that result from the different energy depositions for different ions. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon, neon, silicon and iron ions that were generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS) in Japan. Cell killing was measured as reproductive cell death using a colony formation assay. The RBE-LET curves were different for carbon ions and for the other ions. The curve for carbon ions increased steeply up to around 98 keV/microm. The RBE of carbon ions at 98 keV/microm was 4.07. In contrast, the curves for neon, silicon and iron ions had maximum peaks around 180 keV/microm, and the RBEs at the peak position ranged from 3.03 to 3.39. When the RBEs were plotted as a function of Z*2/beta2 (where Z* is the effective charge and beta is the relative velocity of the ion) instead of LET, the discrepancies between the RBE-LET curves for the different ion beams were reduced, but branching of the RBE-Z*2/beta2 curves still remained. When the inactivation cross section was plotted as a function of either LET or Z*2/beta2, it increased with increasing LET. However, the inactivation cross section was always smaller than the geometrical cross section. These results suggest that the differences in the energy deposition track structures of the different ion sources have an effect on cell killing. 相似文献
109.
110.
Tsutomu Araki Hiroyuki Kato Yasuo Kanai Kyuya Kogure 《Neurochemistry international》1993,23(6):541-548
Age-related alterations in major neurotransmitter receptors and voltage dependent calcium channels were analyzed by receptor autoradiography in the gerbil brain. [3H]Quinuclidinyl benzilate (QNB). [3H]cyclohexyladenosine (CHA), [3H]muscimol, [3H]MK-801, [3H]SCH 23390, [3H]naloxone, and [3H]PN200-110 were used to label muscarinic acetylcholine receptors, adenosine A1 receptors, γ-aminobutyric acidA (GABAA) receptors,
(NMDA) receptors, dopamine D1 receptors, opioid receptors, and voltage dependent calcium channels, respectively. In middle-aged gerbils (16 months old), the hippocampus exhibited a significant elevation in [3H]QNB, [3H]MK-801, [3H]SCH 23390, [3H]naloxone, and [3H]PN200-110 binding, whereas [3H]CHA and [3H]muscimol binding showed a significant reduction in this area, compared with that of young animals (1 month). On the other hand, the cerebellum showed a significant alteration in [3H]QNB, [3H]CHA, and [3H]naloxone binding and the striatum also exhibited a significant alteration in [3H]SCH 23390 and [3H]CHA binding in middle-aged gerbils. The neocortex showed a significant elevation only in [3H]CHA binding in middle-aged animals. The nucleus accumbens and thalamus also showed a significant alteration only in [3H]muscimol binding. However, the hypothalamus and substantia nigra exhibited no significant alteration in these bindings in middle-aged gerbils. These results demonstrate the age-related alterations of various neurotransmitter receptors and voltage dependent calcium channels in most brain regions. Furthermore, they suggest that the hippocampus is most susceptible to aging processes and is altered at an early stage of senescence. 相似文献