全文获取类型
收费全文 | 2138篇 |
免费 | 127篇 |
出版年
2022年 | 11篇 |
2021年 | 12篇 |
2019年 | 14篇 |
2018年 | 18篇 |
2017年 | 16篇 |
2016年 | 30篇 |
2015年 | 52篇 |
2014年 | 50篇 |
2013年 | 115篇 |
2012年 | 82篇 |
2011年 | 70篇 |
2010年 | 55篇 |
2009年 | 48篇 |
2008年 | 72篇 |
2007年 | 77篇 |
2006年 | 90篇 |
2005年 | 89篇 |
2004年 | 99篇 |
2003年 | 87篇 |
2002年 | 89篇 |
2001年 | 75篇 |
2000年 | 73篇 |
1999年 | 73篇 |
1998年 | 27篇 |
1997年 | 32篇 |
1996年 | 26篇 |
1995年 | 22篇 |
1994年 | 19篇 |
1993年 | 23篇 |
1992年 | 54篇 |
1991年 | 60篇 |
1990年 | 46篇 |
1989年 | 48篇 |
1988年 | 46篇 |
1987年 | 35篇 |
1986年 | 39篇 |
1985年 | 34篇 |
1984年 | 30篇 |
1983年 | 31篇 |
1982年 | 26篇 |
1981年 | 17篇 |
1980年 | 17篇 |
1979年 | 20篇 |
1978年 | 15篇 |
1977年 | 17篇 |
1975年 | 15篇 |
1974年 | 21篇 |
1973年 | 11篇 |
1972年 | 11篇 |
1967年 | 16篇 |
排序方式: 共有2265条查询结果,搜索用时 15 毫秒
161.
162.
Yano S Kazuno H Sato T Suzuki N Emura T Wierzba K Yamashita J Tada Y Yamada Y Fukushima M Asao T 《Bioorganic & medicinal chemistry》2004,12(13):3443-3450
A series of novel 6-methylene-bridged uracil derivatives have been optimized for clinical use as the inhibitors of human thymidine phosphorylase (TP). We describe their synthesis and evaluation. Introduction of a guanidino or an amidino group enhanced the in vitro inhibitory activity of TP comparing with formerly reported inhibitor 1. Their selectivity for TP based on uridine phosphorylase inhibitory activity was also evaluated. Compound 2 (TPI) has been selected for clinical evaluation based on its strong TP inhibition and excellent modulation of 2'-deoxy-5-(trifluoromethyl)uridine (F(3)dThd) pharmacokinetics. As a result, TAS-102 (a combination of F(3)dThd and TPI) is currently in phase 1 clinical studies. 相似文献
163.
During a survey of the ciliate protozoal composition of the stomach contents of nine dromedary camels of Egypt, fourteen morphotypes of Entodinium ovumrajae, which has been considered as a species peculiar to camels, were found in six camels. Except for five morphotypes including one originally described as an independent species and its forms, these were newly detected. These morphotypes, divided into three groups, can be identified mainly by the morphology of their ectoplasmic processes. Each camel had on average, about five morphotypes of this species. 相似文献
164.
Teng S Kurata S Katoh I Georgieva GS Nosaka T Mitaka C Imai T 《American journal of physiology. Lung cellular and molecular physiology》2004,286(1):L137-L142
Our aim was to determine whether cytokine mRNA expression is induced by experimental manipulation including artificial perfusate or ischemia-reperfusion (I/R) in an isolated, perfused rat lung model. Constant pulmonary flow [Krebs-Henseleit solution supplemented with low-endotoxin (LE) or standard (ST) bovine serum albumin 4%, 0.04 ml/g body wt] and ventilation were maintained throughout. Right and left pulmonary arteries were isolated, and the left pulmonary artery was occluded for 60 min and then reperfused for 30 min. Analysis of tumor necrosis factor-alpha, IL-1 beta, IL-6, IL-10, and IFN-gamma mRNA expression by RT-PCR and evaluation of vascular permeability by bronchoalveolar lavage (BAL) fluid albumin content were conducted separately in right and left lung. Both LE and ST groups (each 12 rats) showed increases in vascular permeability by I/R (BAL fluid albumin content: 5.53 +/- 1.55 vs. 15.63 +/- 8.87 and 4.76 +/- 2.71 vs. 16.72 +/- 4.85 mg.ml BAL fluid-1.g lung dry wt-1, mean +/- SD; right vs. left lung in LE and ST groups, P < 0.05 between right and left). Cytokine mRNA expression was significantly higher in the I/R lung than in the control lung in the LE group, whereas it was higher in the control lung in the ST group (P < 0.05). mRNAs of not only proinflammatory but also anti-inflammatory cytokines were expressed in I/R lung, which are expected to aggravate I/R injury. The reversed pattern of cytokine mRNA expression in the ST group was possibly due to the longer perfusion of control lung with perfusate containing endotoxin, which caused no lung damage without I/R. 相似文献
165.
Proliferation of donor mitochondrial DNA in nuclear transfer calves (Bos taurus) derived from cumulus cells 总被引:8,自引:0,他引:8
Takeda K Akagi S Kaneyama K Kojima T Takahashi S Imai H Yamanaka M Onishi A Hanada H 《Molecular reproduction and development》2003,64(4):429-437
In embryos derived by nuclear-transfer (NT), fusion of donor cell and recipient oocyte caused mitochondrial heteroplasmy. Previous studies from other laboratories have reported either elimination or maintenance of donor-derived mitochondrial DNA (mtDNA) from somatic cells in cloned animals. Here we examined the distribution of donor mtDNA in NT embryos and calves derived from somatic cells. Donor mitochondria were clearly observed by fluorescence labeling in the cytoplasm of NT embryos immediately after fusion; however, fluorescence diminished to undetectable levels at 24 hr after nuclear transfer. By PCR-mediated single-strand conformation polymorphism (PCR-SSCP) analysis, donor mtDNAs were not detected in the NT embryos immediately after fusion (less than 3-4%). In contrast, three of nine NT calves exhibited heteroplasmy with donor cell mtDNA populations ranging from 6 to 40%. These results provide the first evidence of a significant replicative advantage of donor mtDNAs to recipient mtDNAs during the course of embryogenesis in NT calves from somatic cells. 相似文献
166.
Matsumoto N Tsuruoka S Iwamoto T Tomich JM Ito K Imai M Suzuki M 《The Journal of membrane biology》2003,193(3):195-200
To better understand the process of fluid movement driven by Cl– conductance, a Cl– channel-forming peptide was delivered to the luminal membrane of microperfused rabbit renal proximal tubules. When the peptide (NK4-M2GlyR) was perfused, a significant new conductance was observed within 3 min and stabilized at 10 min. Alteration of the ion composition revealed it to be a Cl–-specific conductance. Reabsorption of Cl– (J
Cl) was increased by NK4-M2GlyR, but not by a scramble NK4-M2GlyR sequence, suggesting that the active peptide formed de novo Cl– channels in the luminal membrane of the perfused tubules. In the presence of the peptide, reabsorption of fluid (J
v) was dramatically increased and J
Na and J
Ca were concomitantly increased. We propose that introduction of the new Cl– conductance in the luminal membrane leads to a coordinated efflux of water across the membrane and an increase in cation translocation via the paracellular pathway, resulting in an increase in J
v. This novel method could prove useful in characterizing mechanisms of fluid transport driven by Cl– gradients. 相似文献
167.
Miyanoiri Y Kobayashi H Imai T Watanabe M Nagata T Uesugi S Okano H Katahira M 《The Journal of biological chemistry》2003,278(42):41309-41315
Musashi1 is an RNA-binding protein abundantly expressed in the developing mouse central nervous system. Its restricted expression in neural precursor cells suggests that it is involved in maintenance of the character of progenitor cells. Musashi1 contains two ribonucleoprotein-type RNA-binding domains (RBDs), RBD1 and RBD2, the affinity to RNA of RBD1 being much higher than that of RBD2. We previously reported the structure and mode of interaction with RNA of RBD2. Here, we have determined the structure and mode of interaction with RNA of RBD1. We have also analyzed the surface electrostatic potential and backbone dynamics of both RBDs. The two RBDs exhibit the same ribo-nucleoprotein-type fold and commonly make contact with RNA on the beta-sheet side. On the other hand, there is a remarkable difference in surface electrostatic potential, the beta-sheet of RBD1 being positively charged, which is favorable for binding negatively charged RNA, but that of RBD2 being almost neutral. There is also a difference in backbone dynamics, the central portion of the beta-sheet of RBD1 being flexible, but that of RBD2 not being flexible. The flexibility of RBD1 may be utilized in the recognition process to facilitate an induced fit. Thus, comparative studies have revealed the origin of the higher affinity of RBD1 than that of RBD2 and indicated that the affinity of an RBD to RNA is not governed by its fold alone but is also determined by its surface electrostatic potential and/or backbone dynamics. The biological role of RBD2 with lower affinity is also discussed. 相似文献
168.
The thermal reactions of the bathoproduct of the long wavelength sensitive visual pigment iodopsin were investigated under various anionic and environmental conditions, to get an insight into the mechanism leading to the unusual thermal isomerization of the retinal chromophore from the trans to the 11-cis form at very low temperatures (-160 degrees C). The all-trans chromophore of the bathoiodopsin produced from iodopsin in the presence of chloride thermally reverted to the 11-cis form, while in the presence of nitrate it kept its all-trans configuration upon warming. Different protein environments, either in a detergent or in phosphatidylcholine (PC) liposomes, did not change the reaction characteristics of the bathoiodopsins under the two anionic conditions. However, reaction characteristics of bathoiodopsins produced in the absence of small anions were dependent on the environment. The trans-to-cis isomerization occurred upon warming of bathoiodopsin in the presence of detergent but not in liposomes. Spectral measurements revealed that iodopsin in the absence of small anions is a mixture of two spectrally distinct forms that exhibit absorption maxima and reaction characteristics similar to those of chloride-bound and nitrate-bound iodopsins, respectively. Thus, iodopsin exhibits two conformational states, each of which is stabilized by the binding of chloride and nitrate, respectively. 相似文献
169.
Siino JS Yau PM Imai BS Gatewood JM Bradbury EM 《Biochemical and biophysical research communications》2003,302(4):885-891
To examine the factors involved with nucleosome stability, we reconstituted nonacetylated particles containing various lengths (192, 162, and 152 base pairs) of DNA onto the Lytechinus variegatus nucleosome positioning sequence in the absence of linker histone. We characterized the particles and examined their thermal stability. DNA of less than chromatosome length (168 base pairs) produces particles with altered denaturation profiles, possibly caused by histone rearrangement in those core-like particles. We also examined the effects of tetra-acetylation of histone H4 on the thermal stability of reconstituted nucleosome particles. Tetra-acetylation of H4 reduces the nucleosome thermal stability by 0.8 degrees C as compared with nonacetylated particles. This difference is close to values published comparing bulk nonacetylated nucleosomes and core particles to ones enriched for core histone acetylation, suggesting that H4 acetylation has a dominant effect on nucleosome particle energetics. 相似文献
170.
Nakamura T Imai H Tsunashima N Nakagawa Y 《Biochemical and biophysical research communications》2003,311(1):139-148
We cloned a full-length cDNA for phospholipid hydroperoxide glutathione peroxidase (PHGPx) including exon Ib from rat and mouse testis. The nuclear signal sequence of the N terminal of rat nuclear PHGPx possessed a different sequence from that previously reported for rat sperm nuclei GPx (SnGPx). Expression of this PHGPx-YFP (yellow fluorescent protein) fusion protein including a novel nuclear signal sequence was exclusively localized in nucleolus; although YFPs fused with only a novel nuclear signal sequence were distributed in the whole nucleus, indicating that preferential translocation of nucleolar PHGPx into nucleoli was required for the nuclear signal sequence and internal sequence of PHGPx. Low level expression of nucleolar PHGPx was detected in several tissues, but the expression of nucleolar PHGPx was extensively high in testis. Immunohistochemical analysis with anti-nucleolar PHGPx indicated that expression of nucleolar PHGPx was observed in the nucleoli in the spermatogonia, spermatocyte, and spermatid. Overexpression of 34kDa nucleolar PHGPx in RBL2H3 cells significantly suppressed cell death induced by actinomycin D and doxorubicin that induced damage in the nucleolus. These results indicated that nucleolar PHGPx plays an important role in prevention of nucleolus from damage in mammalian cells. 相似文献