全文获取类型
收费全文 | 1261篇 |
免费 | 87篇 |
国内免费 | 1篇 |
专业分类
1349篇 |
出版年
2024年 | 6篇 |
2022年 | 15篇 |
2021年 | 13篇 |
2020年 | 9篇 |
2019年 | 12篇 |
2018年 | 12篇 |
2017年 | 17篇 |
2016年 | 20篇 |
2015年 | 34篇 |
2014年 | 45篇 |
2013年 | 73篇 |
2012年 | 71篇 |
2011年 | 77篇 |
2010年 | 44篇 |
2009年 | 44篇 |
2008年 | 83篇 |
2007年 | 76篇 |
2006年 | 74篇 |
2005年 | 86篇 |
2004年 | 90篇 |
2003年 | 81篇 |
2002年 | 83篇 |
2001年 | 18篇 |
2000年 | 12篇 |
1999年 | 25篇 |
1998年 | 14篇 |
1997年 | 20篇 |
1996年 | 15篇 |
1995年 | 12篇 |
1994年 | 9篇 |
1993年 | 12篇 |
1992年 | 14篇 |
1991年 | 18篇 |
1990年 | 10篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 11篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1973年 | 3篇 |
1967年 | 3篇 |
1963年 | 4篇 |
排序方式: 共有1349条查询结果,搜索用时 15 毫秒
71.
Wada H Ura S Kitaoka S Satoh-Asahara N Horie T Ono K Takaya T Takanabe-Mori R Akao M Abe M Morimoto T Murayama T Yokode M Fujita M Shimatsu A Hasegawa K 《PloS one》2011,6(12):e29351
The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, vascular endothelial growth factor-C (VEGF-C) plays a pivotal role in lymphangiogenesis. Circulating levels of VEGF-A and VEGF-C are elevated in sera from obese subjects. However, relationships of VEGF-C with atherosclerotic risk factors and atherosclerosis are unknown. We determined circulating levels of VEGF-A and VEGF-C in 423 consecutive subjects not receiving any drugs at the Health Evaluation Center. After adjusting for age and gender, VEGF-A levels were significantly and more strongly correlated with the body mass index (BMI) and waist circumference than VEGF-C. Conversely, VEGF-C levels were significantly and more closely correlated with metabolic (e.g., fasting plasma glucose, hemoglobin A1c, immunoreactive insulin, and the homeostasis model assessment of insulin resistance) and lipid parameters (e.g., triglycerides, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C)) than VEGF-A. Stepwise regression analyses revealed that independent determinants of VEGF-A were the BMI and age, whereas strong independent determinants of VEGF-C were age, triglycerides, and non-HDL-C. In apolipoprotein E-deficient mice fed a high-fat-diet (HFD) or normal chow (NC) for 16 weeks, levels of VEGF-A were not significantly different between the two groups. However, levels of VEGF-C were significantly higher in HFD mice with advanced atherosclerosis and marked hypercholesterolemia than NC mice. Furthermore, immunohistochemistry revealed that the expression of VEGF-C in atheromatous plaque of the aortic sinus was significantly intensified by feeding HFD compared to NC, while that of VEGF-A was not. In conclusion, these findings demonstrate that VEGF-C, rather than VEGF-A, is closely related to dyslipidemia and atherosclerosis. 相似文献
72.
Prion infection correlates with hypersensitivity of P2X7 nucleotide receptor in a mouse microglial cell line 总被引:1,自引:0,他引:1
Takenouchi T Iwamaru Y Imamura M Kato N Sugama S Fujita M Hashimoto M Sato M Okada H Yokoyama T Mohri S Kitani H 《FEBS letters》2007,581(16):3019-3026
We recently established mouse microglial cells persistently infected with mouse-adapted scrapie ME7 (ScMG20/ME7) for in vitro study of prion pathogenesis. Here, we found that ScMG20/ME7 cells were hypersensitive to P2X7 receptor agonists, as demonstrated by sustained Ca(2+) influx, membrane pore formation, cell death, and interleukin-1beta release. P2X7 mRNA expression was upregulated in these cells, and also in scrapie-infected mice brains. Treatment with pentosan polysulfate eliminated the infectivity and disease-related forms of prion protein from ScMG20/ME7 cell cultures, however, hypersensitivity of P2X7 receptors remained. These results suggest that prion infections may strongly affect the P2X7 receptor system in mouse microglial cells. 相似文献
73.
Mitsuru Iwata Shoko Iwata Mark A. Everett Bryan B. Fuller 《In vitro cellular & developmental biology. Plant》1990,26(6):554-560
Summary A human foreskin organ culture system has been developed to study the response of human skin to hormonal stimulation. Foreskins
are maintained in culture on floating plastic supports which allows the epidermal surface to be exposed to air while the dermis
is bathed in nutrient medium. Both black and white human foreskins can be maintained in organ culture for at least 1 wk with
no change in the tissue structure or cell viability as determined by histochemical staining and by dopa reaction staining.
Tyrosinase activity in both black and white human foreskin cultures decays markedly during the first 2 d of culture to a new
steady state level which remains stable throughout the culture period. Both black and white foreskin cultures consistently
demonstrate 2- to 10-fold increases in tyrosinase activity when treated with theophylline (1 mM). Approximately 90% of all skin cultures examined showed an increase in enzyme activity when treated with this phosphodiesterase
inhibitor. Dibutyryl cAMP (0.1 mM) and [Nle4, D-phe7]-alpha MSH (10−8
M), were also found to markedly stimulate tyrosinase activity in some skin cultures, whereas alpha-MSH and prostaglandin E1 produced only an inconsistent and small increase in the activity of the enzyme. Histamine (1 μM), vitamin D3 (1 μM), and retinoic acid (1μM) failed to stimulate tyrosinase activity in either white or black foreskin cultures. This hormone-responsive organ culture
system can be utilized to characterize the molecular processes responsible for the regulation of tyrosinase and pigmentation
in human skin.
This work was supported by a research contract from the Oklahoma Center for the Advancement of Science and Technology (OCAST)
and by a research grant from the Presbyterian Health Foundation. 相似文献
74.
Abdel Hamid A. Khedr Mamdouh S. Serag Mamdouh M. Nemat-Alla Amina Z. Abo El-Naga Reham M. Nada W. Paul Quick Gaber M. Abogadallah 《Acta Physiologiae Plantarum》2011,33(5):1769-1784
In the present study, Na+ manipulating genes could contribute not only to ion homeostasis but also to growth stimulation with exposing the halophyte
Atriplex halimus L. to moderate NaCl concentration. The stimulation of growth was attributed to Na+ accumulation inside the vacuole leading to increase leaf cell size as well as accelerate leaf cell division. Increasing the
assimilatory surface could result in enhancing the photosynthetic rate. The reduction of A. halimus growth compared to optimum growth at 50 and 200 mM NaCl could be attributed to osmotic effect rather than the ionic one of
salt stress. The inhibition of photosynthesis seemed to be resulted from limitation of CO2 due to the osmotic effect on stomatal conductance rather than the activity loss of photosynthetic machinery. The depletion
of starch content along with the increase in sucrose content could imply that photosynthesis may be a limiting for A. halimus growth. The fast coordinate induction of Na+ manipulating genes could reveal that the tolerance of A. halimus to high concentrations evolved from its ability to regulate and control Na+ influx and efflux. V-H
+-PPase may play a vital role in A. halimus tolerance to osmotic and/or ionic stress due to its kinetics of induction. It seemed that H+-ATPase plays a pivotal role in A. halimus tolerance to stress due to the increase in its protein level was detected with all NaCl concentrations as well as with PEG
treatments. Both of these genes might be useful in improving stress tolerance in transgenic crops. 相似文献
75.
A series of unstable mono- and di-esters of the tetracyclic diterpene ingenol were isolated from the pro-inflammatory ether-soluble fraction of the latex of Euphorbia kamerunica. The esters were isolated by a neutral process involving column and thin-layer chromatography. The monoesters were identified by spectroscopic methods and hydrolysis reactions as ingenol-3-decanoate, ingenol-3-dodecanoate, ingenol-5-hexadienoate and ingenol-5-octenoate and the diesters as 20-acetyl-ingenol-3-octenoate and 20-acetyl-ingenol-3-angelate. 相似文献
76.
Kai W Kikuchi K Fujita M Suetake H Fujiwara A Yoshiura Y Ototake M Venkatesh B Miyaki K Suzuki Y 《Genetics》2005,171(1):227-238
The compact genome of the tiger pufferfish, Takifugu rubripes (fugu), has been sequenced to the "draft" level and annotated to identify all the genes. However, the assembly of the draft genome sequence is highly fragmented due to the lack of a genetic or a physical map. To determine the long-range linkage relationship of the sequences, we have constructed the first genetic linkage map for fugu. The maps for the male and female spanning 697.1 and 1213.5 cM, respectively, were arranged into 22 linkage groups by markers heterozygous in both parents. The resulting map consists of 200 microsatellite loci physically linked to genome sequences spanning approximately 39 Mb in total. Comparisons of the genome maps of fugu, other teleosts, and mammals suggest that syntenic relationship is more conserved in the teleost lineage than in the mammalian lineage. Map comparisons also show a pufferfish lineage-specific rearrangement of the genome resulting in colocalization of two Hox gene clusters in one linkage group. This map provides a foundation for development of a complete physical map, a basis for comparison of long-range linkage of genes with other vertebrates, and a resource for mapping loci responsible for phenotypic differences among Takifugu species. 相似文献
77.
78.
Transformation of L cells with virus thymidine kinase genes introduced by red cell-mediated microinjection 总被引:2,自引:0,他引:2
Takashi Iino Mitsuru Furusawa Iwao Furusawa Masuo Obinata 《Experimental cell research》1983,148(2):475-480
Fusion of red cell ghosts containing foreign materials with cells results in the introduction of the materials into the cells (red cell-mediated microinjection). Until now, 'two-step dialysis' has mainly been used for trapping proteins in the ghosts. Large-sized materials such as DNA, however, are rarely trapped in the ghosts, since the holes in the red cell membrane caused by osmotic shock are too small for such materials to pass through. In this study, we improved the trapping technique. Some of the Hind III fragments of lambda phage DNA as well as proteins could be trapped in the ghosts when the mixture of these materials and red cells were frozen at -80 degrees C for a short period followed by quick thawing. Red cell-mediated microinjection using ghosts containing plasmid pBR322 linked with a Herpes simplex viral thymidine kinase (tk) gene brought about transformation of tk-defective L cells, the efficiency of transformation was 1 out of 20 000-60 000 cells fused with the ghosts. 相似文献
79.
Mozammel Hoque Daniel J. Shea Mitsuru Asada Md. Asad-ud-doullah Motoki Shimizu Ryo Fujimoto Eigo Fukai Keiichi Okazaki 《Molecular breeding : new strategies in plant improvement》2017,37(9):109
The tuberous stem of kohlrabi is an important quantitative trait, which affects its yield and quality. Genetic control of this trait has not yet been unveiled. To identify the QTLs controlling stem swelling of kohlrabi, a BC1 population of 92 plants was developed from a cross of broccoli DH line GCP04 and kohlrabi var. Seine. A wide range of variation in tuberous stem diameter was observed among the mapping populations. We constructed a genetic map of nine linkage groups (LGs) with different types of markers, spanning a total length of 913.5 cM with an average marker distance of 7.55 cM. Four significant QTLs for radial enlargement of kohlrabi stem, namely, REnBo1, REnBo2, REnBo3, and REnBo4 were detected on C02, C03, C05, and C09, respectively, and accounted for the phenotypic variation of 59% for the stem diameter and 55% for the qualitative grading of tuberous stem in classes. Then, we confirmed the stability of identified QTLs using BC1S1 populations derived from the BC1 plants having heterozygous alleles at the target QTL and homozygous kohlrabi alleles at the remaining QTLs. REnBo1and REnBo2 using 128 plants of BC168S1 and 94 plants of BC143S1, respectively, and REnBo3 and REnBo4 using 152 plants of BC157S1 were detected at the same positions as the respective QTLs of the BC1 population. Confirmation of QTLs in two successive generations indicates that the QTLs are persistent. The QTLs obtained in this study could be useful in marker-assisted selection of kohlrabi breeding, and to understand the genetic mechanisms of stem swelling and storage organ development in kohlrabi and other Brassica species. 相似文献
80.
Hashigasako A Machide M Nakamura T Matsumoto K Nakamura T 《The Journal of biological chemistry》2004,279(25):26445-26452
Previous studies indicated that treatment of cells with 12-O-tetradecanoylphorbol-13-acetate induced phosphorylation of Ser-985 at the juxtamembrane of c-Met, the receptor tyrosine kinase for hepatocyte growth factor (HGF), and this was associated with decreased tyrosine phosphorylation of c-Met. However, the regulatory mechanisms and the biological significance of the Ser-985 phosphorylation in c-Met remain unknown. When A549 human lung cancer cells were exposed to oxidative stress with H(2)O(2), H(2)O(2) treatment induced phosphorylation of Ser-985, but this was abrogated by an inhibitor for protein kinase C (PKC). Likewise, treatment of cells with NaF (an inhibitor of protein phosphatases) allowed for phosphorylation of Ser-985, and a protein phosphatase responsible for dephosphorylation of Ser-985 was identified to be protein phosphatase 2A (PP2A). The effects of PKC inhibitors revealed that PKCdelta and -epsilon were responsible for the Ser-985 phosphorylation of c-Met, and pull-down analysis indicated that associations of PKCdelta and -epsilon with c-Met may be involved in the regulation of Ser-985 phosphorylation of c-Met. Instead, PP2A was constitutively associated with c-Met, whereas its activity to dephosphorylate Ser-985 of c-Met was decreased when cells were exposed to H(2)O(2). Addition of HGF to A549 cells in culture induced c-Met tyrosine phosphorylation, the result being mitogenic response and cell scattering. In contrast, in the presence of H(2)O(2) stress, HGF-dependent tyrosine phosphorylation of c-Met was largely suppressed with a reciprocal relationship to Ser-985 phosphorylation, and this event was associated with abrogation of cellular responsiveness to HGF. These results indicate that Ser-985 phosphorylation of c-Met is bi-directionally regulated through PKC and PP2A, and the Ser-985 phosphorylation status may provide a unique mechanism that confers cellular responsiveness/unresponsivenss to HGF, depending on extracellular conditions. 相似文献