全文获取类型
收费全文 | 1291篇 |
免费 | 109篇 |
出版年
2022年 | 8篇 |
2021年 | 12篇 |
2020年 | 17篇 |
2019年 | 13篇 |
2018年 | 24篇 |
2017年 | 17篇 |
2016年 | 26篇 |
2015年 | 27篇 |
2014年 | 42篇 |
2013年 | 66篇 |
2012年 | 84篇 |
2011年 | 81篇 |
2010年 | 42篇 |
2009年 | 41篇 |
2008年 | 77篇 |
2007年 | 93篇 |
2006年 | 83篇 |
2005年 | 80篇 |
2004年 | 86篇 |
2003年 | 72篇 |
2002年 | 60篇 |
2001年 | 13篇 |
2000年 | 24篇 |
1999年 | 18篇 |
1998年 | 12篇 |
1997年 | 14篇 |
1996年 | 13篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 9篇 |
1991年 | 19篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 16篇 |
1987年 | 6篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 12篇 |
1980年 | 13篇 |
1979年 | 14篇 |
1978年 | 13篇 |
1977年 | 6篇 |
1976年 | 6篇 |
1975年 | 12篇 |
1973年 | 5篇 |
1971年 | 6篇 |
排序方式: 共有1400条查询结果,搜索用时 31 毫秒
121.
Hattori J Okumura N Yamazaki Y Uchiyama M Hamaguchi M Nishiyama Y Kaneda T 《Microbiology and immunology》2007,51(2):193-200
Several reports have documented a better prognosis for HIV‐1‐infected patients co‐infected with GBV‐C, while other reports have contradicted such findings with the result that this issue remains controversial. We attempted to clarify the complicated status of the effect of GBV‐C co‐infection on HIV‐1‐infected patients. GBV‐C RNA was detected in 37 samples in 182 HIV‐1‐infected patients (20.3%) using RT/nested PCR. Of these, 3 were determined to be GBV‐C genotype 1, 12 were genotype 2, and the remaining 22 were genotype 3. The GBV‐C viral load quantified by real‐time PCR ranged from 7.8 × 103 to 3.3 × 106 copies/ml. Weakly negative correlation was observed between GBV‐C viral load and HIV‐1 viral load in 19 HAART‐naïve patients, indicating that a higher GBV‐C viral load is associated with a greater suppression of HIV‐1 replication. A previously published in vitro study suggested that GBV‐C infection would induce up‐regulation of RANTES, leading to suppression of HIV‐1 replication. However, in our present study, the blood RANTES level was significantly lower in the GBV‐C co‐infected group than in the uninfected group (190–9,959 vs. 264–31,038 pg/ml, P=0.004). Our results suggested that a suppression of HIV‐1 replication by GBV‐C co‐infection is not mediated by up‐regulated RANTES, and thus call for another as yet unknown factor. 相似文献
122.
We have previously reported that protein kinase C gamma (PKC-gamma) is activated by phorbol-12-myristate-13-acetate (TPA) and that this causes PKC-gamma translocation to membranes and phosphorylation of the gap junction protein, connexin 43 (Cx43). This phosphorylation, on S368 of Cx43, causes disassembly of Cx43 out of cell junctional plaques resulting in the inhibition of dye transfer. The purpose of this study is to identify the specific role of zonula occludens protein-1 (ZO-1), a tight junction protein with recently established effects on gap junctions, in this PKC-gamma-driven Cx43 disassembly. For this purpose, ZO-1 levels in lens epithelial cells in culture were decreased by up to 70% using specific siRNA. The down-regulation of ZO-1 caused a stable interaction of PKC-gamma with Cx43 even without normal enzyme activation by TPA. However, after TPA activation of the PKC-gamma, the Cx43 did not disassemble out of plaques even though the PKC-gamma enzyme was activated and the Cx43 was phosphorylated on S368. Confocal microscopy demonstrated that the siRNA treatment caused a loss of ZO-1 from borders of large junctional Cx43 cell-to-cell plaques and resulted in the accumulation of Cx43 aggregates inside of cells. Loss of the specific "plaquetosome" arrangement of large Cx43 plaques surrounded by ZO-1 was accompanied by a complete loss of functional dye transfer. These results suggest that ZO-1 is required for Cx43 control, both for dye transfer, and, for the PKC-gamma-driven disassembly response. 相似文献
123.
Takemoto D Takekawa Y Soest RW Fusetani N Matsunaga S 《Bioscience, biotechnology, and biochemistry》2007,71(11):2697-2700
Poecillastrin D (2) was isolated together with poecillastrin C (1) from the deep sea sponge, Japsis serpentina. Its structure was elucidated to be that of a macrolide lactam by spectroscopic methods. These compounds showed potent cytotoxicity against various tumor cell lines. 相似文献
124.
125.
How did bonobos come to range south of the congo river? Reconsideration of the divergence of Pan paniscus from other Pan populations
下载免费PDF全文
![点击此处可从《Evolutionary anthropology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
While investigating the genetic structure in wild bonobos,1 we realized that the widely accepted scenario positing that the Pleistocene appearance of the Congo River separated the common ancestor of chimpanzees (Pan troglodytes) and bonobos (P. paniscus) into two species is not supported by recent geographical knowledge about the formation of the Congo River. We explored the origin of bonobos using a broader biogeographical perspective by examining local faunas in the central African region. The submarine Congo River sediments and paleotopography of central Africa show that the Congo River has functioned as a geographical barrier for the last 34 million years. This evidence allows us to hypothesize that when the river was first formed, the ancestor of bonobos did not inhabit the current range of the species on the left bank of the Congo River but that, during rare times when the Congo River discharge decreased during the Pleistocene, one or more founder populations of ancestral Pan paniscus crossed the river to its left bank. The proposed scenario for formation of the Congo River and the corridor hypothesis for an ancestral bonobo population is key to understanding the distribution of great apes and their evolution. 相似文献
126.
Miyata Seiko Noda Akiko Iwamoto Kunihiro Kawano Naoko Banno Masahiro Tsuruta Yoshiyuki Noda Yukihiro Ozaki Norio 《Sleep and biological rhythms》2015,13(4):387-394
Sleep and Biological Rhythms - Chronic sleep restriction adversely effects cognitive performance and mood, resulting in accidents and economic loss. We examined the effects of three nights of sleep... 相似文献
127.
Nagai H Goto T Takahashi N Kusudoh T Deyashiki Y Esaka Y Kawada T 《Bioscience, biotechnology, and biochemistry》2011,75(8):1485-1489
A useful method employing liquid chromatography mass spectrometry (LC/MS) and a stable isotope was developed for simultaneous examination of major metabolism in adipocytes, de novo fatty acid synthesis, glycerol output, and glucose uptake with high sensitivity. The addition of thiazolidinediones, potent agonists of peroxisome proliferator-activated receptors-γ, for 10 d increased glucose uptake in a dose-dependent manner. Fatty acid (FA) synthesis increased at low concentrations of thiazolidinediones (TZDs) and decreased at high concentrations. It is important to assess adipocytes from various examples of metabolism, because each example of adipocyte metabolism is directly related to obesity or metabolic syndrome in various ways. The technique makes metabolic examination easier than conventional methods by means of radioisotopes and makes it possible to identify metabolites and to apply them in biomarker screening. 相似文献
128.
Itoh Y Kitaguchi R Ishikawa M Naito M Hashimoto Y 《Bioorganic & medicinal chemistry》2011,19(22):6768-6778
Compounds that regulate the function(s) of nuclear receptors (NRs) are useful for biological studies and as candidate therapeutic agents. Most such compounds are agonists or antagonists. On the other hand, we have developed specific protein degradation inducers, which we designated as SNIPERs (Specific and Nongenetic IAPs-dependent Protein ERasers), for selective degradation of target proteins. SNIPERs are hybrid molecules consisting of an appropriate ligand for the protein of interest, coupled to a ligand for inhibitor of apoptosis proteins (IAPs), which target the bound protein for polyubiquitination and proteasomal degradation. We considered that protein knockdown with SNIPERs would be a promising alternative approach for modulating NR function. In this study, we designed and synthesized degradation inducers targeting retinoic acid receptor (RAR), estrogen receptor (ER), and androgen receptor (AR). These newly synthesized RAR, ER, and AR SNIPERs, 9, 11, and 13, respectively, were confirmed to significantly reduce the levels of the corresponding NRs in live cells. 相似文献
129.
Yoshida M Mori A Morimoto S Kotani E Oka M Notoya K Makino H Ono M Shirasaki M Tada N Fujita H Ban J Ikeda Y Kawamoto T Goto M Kimura H Baba A Yasuma T 《Bioorganic & medicinal chemistry》2011,19(6):1881-1894
The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. 相似文献
130.
Junko Morimoto Kento Hirabayashi Emu Mizumoto Takehiko Katsuno Yukihiro Morimoto 《Landscape and Ecological Engineering》2011,7(2):185-193
To develop an appropriate method of conservation for native Rhododendron sections Brachycalyx and Tsutsusi, the symbol of Satoyama, field experiments were performed in the dry granite region of Japan. When carpet-type landscape
of native rhododendrons was desired, all plants were cut at 20 cm above the ground level of all trees and shrubs, and herbs
and ferns were weeded (once and three times, respectively). When shrubby-type landscape of native rhododendrons was desired,
all plants, excluding native rhododendrons, were cut at 20 cm above the ground level of all trees and shrubs, herbs and ferns
were weeded, and litter was swept. After 3 years of monitoring of the percentage and depth of crowns with flower buds, the
following major results were obtained: Cutting all plants excluding native rhododendrons was effective to maintain the depth
of crowns with flower buds. However, weeding and sweeping of litter on the ground caused desiccation of surface soil, which
induced a transitory decrease in the percentage of crowns with flower buds. One weeding was effective in maintaining the depth
of crowns with flower buds; however, the second and third weedings had no distinct effect. In dry granite regions, considerable
attention to desiccation of surface soil is critical, as opposed to limiting attention to maintenance of sunlight as is common
practice. 相似文献