全文获取类型
收费全文 | 737篇 |
免费 | 40篇 |
专业分类
777篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 12篇 |
2014年 | 13篇 |
2013年 | 42篇 |
2012年 | 46篇 |
2011年 | 42篇 |
2010年 | 14篇 |
2009年 | 19篇 |
2008年 | 65篇 |
2007年 | 59篇 |
2006年 | 54篇 |
2005年 | 60篇 |
2004年 | 64篇 |
2003年 | 42篇 |
2002年 | 36篇 |
2001年 | 16篇 |
2000年 | 8篇 |
1999年 | 11篇 |
1998年 | 13篇 |
1997年 | 11篇 |
1996年 | 5篇 |
1995年 | 9篇 |
1994年 | 6篇 |
1993年 | 9篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 2篇 |
1982年 | 11篇 |
1981年 | 8篇 |
1980年 | 4篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1964年 | 1篇 |
1926年 | 1篇 |
排序方式: 共有777条查询结果,搜索用时 0 毫秒
31.
Philip J. Bergmann Gen Morinaga Elyse S. Freitas Duncan J. Irschick Günter P. Wagner Cameron D. Siler 《Proceedings. Biological sciences / The Royal Society》2020,287(1938)
Evolutionary reversals, including re-evolution of lost structures, are commonly found in phylogenetic studies. However, we lack an understanding of how these reversals happen mechanistically. A snake-like body form has evolved many times in vertebrates, and occasionally a quadrupedal form has re-evolved, including in Brachymeles lizards. We use body form and locomotion data for species ranging from snake-like to quadrupedal to address how a quadrupedal form could re-evolve. We show that large, quadrupedal species are faster at burying and surface locomotion than snake-like species, indicating a lack of expected performance trade-off between these modes of locomotion. Species with limbs use them while burying, suggesting that limbs are useful for burying in wet, packed substrates. Palaeoclimatological data suggest that Brachymeles originally evolved a snake-like form under a drier climate probably with looser soil in which it was easier to dig. The quadrupedal clade evolved as the climate became humid, where limbs and large size facilitated fossorial locomotion in packed soils. 相似文献
32.
The redox environment of the cell is currently thought to be extremely important to control either apoptosis or autophagy. This study reported that reactive oxygen species (ROS) and nitric oxide (NO) generations were induced by evodiamine time-dependently; while they acted in synergy to trigger mitochondria-dependent apoptosis by induction of mitochondrial membrane permeabilization (MMP) through increasing the Bax/Bcl-2 or Bcl-xL ratio. Autophagy was also stimulated by evodiamine, as demonstrated by the positive autophagosome-specific dye monodansylcadaverine (MDC) staining as well as the expressions of autophagy-related proteins, Beclin 1 and LC3. Pre-treatment with 3-MA, the specific inhibitor for autophagy, dose-dependently decreased cell viability, indicating a survival function of autophagy. Importantly, autophagy was found to be promoted or inhibited by ROS/NO in response to the severity of oxidative stress. These findings could help shed light on the complex regulation of intracellular redox status on the balance of autophagy and apoptosis in anti-cancer therapies. 相似文献
33.
Muichi Kaito Shin-Ichi Araya Yuichiro Gondo Michiyo Fujita Naomi Minato Megumi Nakanishi Makoto Matsui 《PloS one》2013,8(8)
Background and Purpose
The most common strategy for treating patients with acute ischemic stroke is thrombolytic therapy, though only a few patients receive benefits because of the narrow time window. Inflammation occurring in the central nervous system (CNS) in association with ischemia is caused by immune cells including monocytes and involved in lesion expansion. If the specific roles of monocyte subsets in stroke can be revealed, they may become an effective target for new treatment strategies.Methods
We performed immunological examinations of 36 consecutive ischemic stroke patients within 2 days of onset and compared the results with 24 age-matched patients with degenerative disorders. The stroke patients were repeatedly tested for the proportions of monocyte subsets in blood, and serum levels of pro- and anti-inflammatory cytokines immediately after admission, on days 3-7 and 12-16 after stroke onset, and on the day of discharge. In addition, immunological measurements were analyzed for relationships to stroke subtypes and complications, including progressive infarction (PI) and stroke-associated infection (SAI).Results
Monocyte count was significantly increased from 0–16 days after stroke as compared to the controls (p<0.05). CD14highCD16- classical and CD14highCD16+ intermediate monocytes were significantly increased from 0-7 and 3-16 days after stroke, respectively (p<0.05), whereas CD14 dimCD16high non-classical monocytes were decreased from 0–7 days (p<0.05). Cardioembolic infarction was associated with a persistent increase in intermediate monocytes. Furthermore, intermediate monocytes were significantly increased in patients with PI (p<0.05), while non-classical monocytes were decreased in those with SAI (p<0.05). IL-17A levels were positively correlated with monocyte count (r=0.485, p=0.012) as well as the percentage of non-classical monocytes (r=0.423, p=0.028), and negatively with that of classical monocytes (r=-0.51, p=0.007) during days 12-16.Conclusions
Our findings suggest that CD14highCD16+ intermediate monocytes have a role in CNS tissue damage during acute and subacute phases in ischemic stroke especially in relation to cardioembolism. 相似文献34.
35.
Isamu Shiio Yasuhiko Toride Shin-Ichi Sugimoto 《Bioscience, biotechnology, and biochemistry》2013,77(12):3091-3098
Mutants with low pyruvate dehydrogenase (PD) activities were derived from a pyruvate kinase-deficient lysine-producing mutant of Brevibacterium flavum, No. 22. They were selected as prototrophic revertants of the acetate auxotrophs of strain No. 22. Among them strain KD-11 produced 55g/liter of lysine as its HCI salt when cultured for 72 hr in a medium containing lOOg/liter of glucose, soybean-meal hydrolysate and methionine. The lysine yield of strain KD-11 was the highest ever reported (55%). The mutant required a higher concentration of methionine for maximum production and gave a smaller amount of cell mass in cultivation than its parent. PD activity of strain No. 22 was stimulated by cysteine, stabilized by glycerol, and gave apparent Kms of 89, 22, 380, 83 μM for pyruvate, coenzyme A, 3-acetylpyridine adenine dinucleotide, and NAD, respectively, under standard conditions. The apparent Km for NAD of PD from strain KD-11 was 10-times higher than that from No. 22. When the concentration of NAD was low, the cell extracts of strain KD-11 showed low PD activity. The specific activity of phosphoenolpyruvate carboxylase of strain KD-11 was slightly higher than that of strain No. 22, while the inhibition by aspartate of the former enzyme was weaker than that of the latter. 相似文献
36.
Hirofumi Inoue Ken-Ichi Kobayashi Moussa Ndong Yuji Yamamoto Shin-Ichi Katsumata Kazuharu Suzuki 《Bioscience, biotechnology, and biochemistry》2013,77(8):1366-1368
We investigated the effects of dietary iron deficiency on the redox system in the heart. Dietary iron deficiency increased heart weight and accumulation of carbonylated proteins. However, expression levels of heme oxygenase-1 and LC3-II, an antioxidant enzyme and an autophagic marker, respectively, in iron-deficient mice were upregulated compared to the control group, resulting in a surrogate phenomenon against oxidative stress. 相似文献
37.
Kazuki Sato Hiroyuki Anaguchi Komei Kobayashi Taeko Morinaga Naoyuki Nishimura Yasuo Kobayashi 《Bioscience, biotechnology, and biochemistry》2013,77(8):2047-2053
Temperature-sensitive sporulation mutants were isolated spontaneously from Bacillus subtilis 168 TT by a sequential transfer method. A representative mutant strain, ts32, was characterized in detail. The mutant grew normally at 30°C and 42°C, but did not sporulate at 42°C. Electron microscopic observation and physiological analysis showed that the mutant was blocked at stage 0-1 of sporulation. Genetic analysis suggested that the mutation was located at the spo0B locus on the B. subtilis chromosome. Temperature-shift experiments clearly showed that the spo0B gene product functions only at the beginning of sporulation. 相似文献
38.
Yasuhiro Arii Kohei Butsusihta Shin-Ichi Fukuoka 《Bioscience, biotechnology, and biochemistry》2013,77(6):978-985
Annexin A4 (Anx4) is a cytosolic calcium-binding protein with four repeat domains, each containing one calcium-binding site (CBS). The protein interacts with the phospholipid membrane through the CBS-coordinated calcium ion, although the role of each CBS in the calcium-dependent association is unclear. To determine the role of each CBS, 15 CBS-abolished variants were produced in various combinations by substitution of a calcium-liganding residue on each CBS by Ala. Various mutant combinations produced different influences on calcium-dependent membrane-binding behavior and on the sodium-dependent dissociation of membrane-bound Anx4. Our data suggest the interaction of Anx4 with the lipid membrane consists of strong and weak interactions. CBSs I and IV mediate formation of strong interactions, while CBSs II and III are important for weak interactions. We also suggest Anx4 binds the lipid membrane through CBSs I and IV in the cytoplasmic fluids. 相似文献
39.
Ito S Ihara T Tamura H Tanaka S Ikeda T Kajihara H Dissanayake C Abdel-Motaal FF El-Sayed MA 《FEBS letters》2007,581(17):3217-3222
The tomato saponin alpha-tomatine has been proposed to kill sensitive cells by binding to cell membranes followed by leakage of cell components. However, details of the modes of action of the compound on fungal cells are poorly understood. In the present study, mechanisms involved in alpha-tomatine-induced cell death of fungi were examined using a filamentous pathogenic fungus Fusarium oxysporum. alpha-Tomatine-induced cell death of F. oxysporum (TICDF) occurred only under aerobic conditions and was blocked by the mitochondrial F(0)F(1)-ATPase inhibitor oligomycin, the caspase inhibitor D-VAD-fmk, and protein synthesis inhibitor cycloheximide. Fungal cells exposed to alpha-tomatine showed TUNEL-positive nuclei, depolarization of transmembrane potential of mitochondria, and reactive oxygen species (ROS) accumulation. These results suggest that TICDF occurs through a programmed cell death process in which mitochondria play a pivotal role. Pharmacological studies using inhibitors suggest that alpha-tomatine activates phosphotyrosine kinase and monomeric G-protein signaling pathways leading to Ca(2+) elevation and ROS burst in F. oxysporum cells. 相似文献
40.
Takaaki Kameji Yasuko Murakami Kazunobu Fujita Shin-Ichi Hayashi 《Biochimica et Biophysica Acta (BBA)/General Subjects》1982,717(1):111-117
Ornithine decarboxylase (EC 4.1.1.17) was purified to near homogeniety from livers of thioacetamide- and dl-α-hydrazino-δ-aminovaleric acid-treated rats by using three types of affinity chromatography with pyridoxamine phosphate-Sepharose, pyridoxamine phosphate-dipropylenetriamine-Sepharose and heparin-Sepharose. This procedure gave a purification of about 3.5·105-fold with an 8% yield; the specific activity of the final enzyme preparation was 1,1·106 nmol CO2/h per mg protein. The purified enzyme gave a single band of protein which coincided with activity peak on polyacrylamide gel electrophoresis and also gave a single major band on SDS-polyacrylamide gel electrophoresis. A single precipitin line was formed between the purified enzyme and an antiserum raised against a partially purified enzyme, on Ouchterlony immunodiffusion. The molecular weight of the enzyme was estimated to be 105 000 by polyacrylamide gel electrophoresis at several different gel concentrations; the dissociated subunits had molecular weights of 50 000 on SDS-polyacrylmide gels. The isoelectric point of the enzyme was pH 4.1. 相似文献