全文获取类型
收费全文 | 2206篇 |
免费 | 219篇 |
国内免费 | 1篇 |
专业分类
2426篇 |
出版年
2023年 | 4篇 |
2022年 | 15篇 |
2021年 | 36篇 |
2020年 | 21篇 |
2019年 | 29篇 |
2018年 | 24篇 |
2017年 | 31篇 |
2016年 | 66篇 |
2015年 | 89篇 |
2014年 | 85篇 |
2013年 | 114篇 |
2012年 | 185篇 |
2011年 | 167篇 |
2010年 | 110篇 |
2009年 | 74篇 |
2008年 | 173篇 |
2007年 | 156篇 |
2006年 | 157篇 |
2005年 | 137篇 |
2004年 | 124篇 |
2003年 | 120篇 |
2002年 | 160篇 |
2001年 | 30篇 |
2000年 | 23篇 |
1999年 | 31篇 |
1998年 | 42篇 |
1997年 | 12篇 |
1996年 | 16篇 |
1995年 | 17篇 |
1994年 | 21篇 |
1993年 | 14篇 |
1992年 | 18篇 |
1991年 | 13篇 |
1990年 | 8篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 12篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1967年 | 2篇 |
排序方式: 共有2426条查询结果,搜索用时 11 毫秒
71.
Philip J. Robinson Cheryl A. Woolhead 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2013,1833(12):2781-2788
Membrane protein insertion is controlled by proteinaceous factors embedded in the lipid bilayer. Bacterial inner membrane proteins utilise the Sec translocon as the major facilitator of insertion; however some proteins are Sec independent and instead require only YidC. A common feature of YidC substrates is the exposure of a signal anchor sequence when translation is close to completion; this allows minimal time for targeting and favours a post-translational insertion mechanism. Despite this there is little evidence of YidC's post-translational activity. Here we develop an experimental system that uncouples translation and insertion of the endogenous YidC substrate F0c (subunit c of the F0F1 ATP synthase). In this process we (i) develop a novel one step purification method for YidC, including an on column membrane reconstitution, (ii) isolate a soluble form of F0c and (iii) show that incubation of F0c with YidC proteoliposomes results in a high level of membrane integration. Conformational analyses of inserted F0c through Blue Native PAGE and fluorescence quenching reveal a native, oligomerised structure. These data show that YidC can act as a post-translational insertase, a finding which could explain the absence of a ribosome binding domain on YidC. This correlates with the post-translational activity of other YidC family members lacking the ribosome binding domain. 相似文献
72.
As a reported agonist,11C-CUMI-101 is believed to selectively bind the G-protein-coupled state of the serotonin-1A (5-HT1A) receptor, thereby providing a measure of the active subset of all 5-HT1A receptors in brain. Although 11C-CUMI-101 has been successfully used to quantify 5-HT1A receptors in human and monkey brain, its radiation exposure has not previously been reported. The purpose of this study was to calculate the radiation exposure to organs of the body based on serial whole-body imaging with positron emission tomography (PET) in human subjects.
Methods
Nine healthy volunteers were injected with 428±84 MBq (mean ± SD) 11C-CUMI-101 and then imaged with a PET-only device for two hours from head to mid-thigh. Eleven source organs (brain, heart, liver, pancreas, stomach, spleen, lungs, kidneys, lumbar spine L1-5, thyroid, and urinary bladder) were identified on whole body images and used to calculate radiation doses using the software program OLINDA/EXM 1.1. To confirm that we had correctly identified the pancreas, a tenth subject was imaged on a PET/CT device.Results
Brain had high uptake (∼11% of injected activity (IA)) at 10 min. Although liver had the highest uptake (∼35% IA at 120 min), excretion of this activity was not visible in gall bladder or intestine during the scanning session. Organs which received the highest doses (microSv/MBq) were pancreas (32.0), liver (18.4), and spleen (14.5). The effective dose of 11C-CUMI-101 was 5.3±0.5 microSv/MBq.Conclusion
The peak brain uptake (∼11% IA) of 11C-CUMI-101 is the highest among more than twenty 11C-labeled ligands reported in the literature and provides good counting statistics from relatively low injected activities. Similar to that of other 11C-labeled ligands for brain imaging, the effective dose of 11C-CUMI-101 is 5.3±0.5 microSv/MBq, a value that can now be used to estimate the radiation risks in future research studies. 相似文献73.
Gerald J. Putterman Badaruddin Shaikh Margarette R. Hallmark Cheryl G. Sawyer Catherine V. Hixson Fulvio Perini 《Analytical biochemistry》1979,98(1):18-26
Procedures are presented for the simultaneous analysis of hypoxanthine, xanthine, allopurinol, oxipurinol, and uric acid in standard mixtures and physiological fluids using gas chromatography (gc) or high-pressure liquid chromatography (hplc). Excellent correlation was obtained between the two methods for hypoxanthine, xanthine, oxipurinol, and uric acid. There are advantages and disadvantages to both methods. hplc requires no prior derivatization, uses isocratic elution with a buffer containing no organic solvent, and has 50- to 100-fold greater sensitivity than gc. Simpler methods of prepurification, readily adapted to clinical laboratories, can be used for hplc analysis. Although substances that are found in some urine samples from cancer patients interfere with hplc, separations by gc are not affected by these substances. 相似文献
74.
Danielle Julie Carrier Cheryl A. Bock James E. Cunningham David R. Cyr David I. Dunstan 《In vitro cellular & developmental biology. Plant》1997,33(3):236-239
Summary Interior spruce (Picea glauca engelmannii complex) somatic embryos grown on 48 μmol (±)-ABA per L over a period of 42 d without transfer underwent precocious germination
by 49 d. Those transferred at 28 d to fresh medium with 48 μmol (±)-ABA continued embryo development until harvested at 56
d; the transfer at 28 d resulted in an increase in embryo lipid content after 42 d. Somatic embryos grown under this condition
contained 181.4±41.2, 116.0±42.4, and 91.8±33.6 ng (+)-ABA per mg of lyophilized tissue at 42, 49, and 56 d, respectively.
By comparison, embryos grown without the transfer at 28 d had 86.8±25.4 ng (+)-ABA per mg of lyophilized tissue at 42 d, just
prior to precocious germination. After 3 weeks’ storage in a drying chamber under high humidity, the (+)-ABA content of 56-d-old
transferred embryos decreased to 15.4 ± 4.4 ng (+)-ABA per mg of lyophilized tissue. The increased lipid content resulting
from embryo transfer and the reduction in internal (+)-ABA content during storage are factors which will contribute to improved
conversion of somatic embryos to plantlets. 相似文献
75.
Common bacterial responses in six ecosystems exposed to 10 years of elevated atmospheric carbon dioxide 总被引:1,自引:0,他引:1
Dunbar J Eichorst SA Gallegos-Graves LV Silva S Xie G Hengartner NW Evans RD Hungate BA Jackson RB Megonigal JP Schadt CW Vilgalys R Zak DR Kuske CR 《Environmental microbiology》2012,14(5):1145-1158
Six terrestrial ecosystems in the USA were exposed to elevated atmospheric CO(2) in single or multifactorial experiments for more than a decade to assess potential impacts. We retrospectively assessed soil bacterial community responses in all six-field experiments and found ecosystem-specific and common patterns of soil bacterial community response to elevated CO(2) . Soil bacterial composition differed greatly across the six ecosystems. No common effect of elevated atmospheric CO(2) on bacterial biomass, richness and community composition across all of the ecosystems was identified, although significant responses were detected in individual ecosystems. The most striking common trend across the sites was a decrease of up to 3.5-fold in the relative abundance of Acidobacteria Group 1 bacteria in soils exposed to elevated CO(2) or other climate factors. The Acidobacteria Group 1 response observed in exploratory 16S rRNA gene clone library surveys was validated in one ecosystem by 100-fold deeper sequencing and semi-quantitative PCR assays. Collectively, the 16S rRNA gene sequencing approach revealed influences of elevated CO(2) on multiple ecosystems. Although few common trends across the ecosystems were detected in the small surveys, the trends may be harbingers of more substantive changes in less abundant, more sensitive taxa that can only be detected by deeper surveys. Representative bacterial 16S rRNA gene clone sequences were deposited in GenBank with Accession No. JQ366086–JQ387568. 相似文献
76.
David A. Scott Kirsten J. Bell Cheryl T. Campbell Donald J. Cook Les A. Dakin David J. Del Valle Lisa Drew Thomas W. Gero Maureen M. Hattersley Charles A. Omer Boris Tyurin Xiaolan Zheng 《Bioorganic & medicinal chemistry letters》2009,19(3):701-705
The optimization of compounds from the 3-amido-4-anilinoquinolines series of CSF-1R kinase inhibitors is described. The series has excellent activity and kinase selectivity. Excellent physical properties and rodent PK profiles were achieved through the introduction of cyclic amines at the quinoline 6-position. Compounds with good activity in a mouse PD model measuring inhibition of pCSF-1R were identified. 相似文献
77.
RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism 下载免费PDF全文
Aslanukov A Bhowmick R Guruju M Oswald J Raz D Bush RA Sieving PA Lu X Bock CB Ferreira PA 《PLoS genetics》2006,2(10):e177
The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2−/− are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2+/− mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies. 相似文献
78.
Jones HN Ashworth CJ Page KR McArdle HJ 《American journal of physiology. Endocrinology and metabolism》2006,291(3):E596-E603
Both placental system A activity and fetal plasma cortisol concentrations are associated with intrauterine growth retardation, but it is not known if these factors are mechanistically related. Previous functional studies using hepatoma cells and fibroblasts produced conflicting results regarding the regulation of system A by cortisol. Using the b30 BeWo choriocarcinoma cell line, we investigated the regulation of system A by cortisol. System A function was analyzed using methyl amino isobutyric acid (MeAIB) transcellular transport studies. Transporter expression [system A transporter (SNAT)1/2] was studied at the mRNA and protein levels using Northern and Western blotting, respectively. Localization was carried out using immunocytochemistry. The [(14)C]MeAIB transfer rate across BeWo monolayers after preincubation with cortisol for 24 h was significantly increased compared with control. This was associated with a relocalization of the SNAT2 transporter at lower cortisol levels and significant upregulation of mRNA and protein expression levels at cortisol levels >1 microM. This is the first study to show functional and molecular regulation of system A by cortisol in BeWo cells. It is also the first study to identify which system A isoform is regulated. These results suggest that cortisol may be involved in upregulation of system A in the placenta to ensure sufficient amino acid supply to the developing fetus. 相似文献
79.
80.
The specific activity of creatine phosphokinase (CPK) was measured in the muscle of mdg/mdg and control embryos of 14-18 days' gestation. CPK specific activity values were similar in mutant and normal embryos at the earliest stages examined (14-15 days). However, after 15 1/2 days, the specific activity of the enzyme in the mdg/mdg embryos was approximately 50% lower than in the controls. The dysgenic and normal muscle extracts exhibited comparable stability after storage at -85 C. CPK activity levels in the muscle of adult heterozygotes (+/mdg) and wild-type (+/+) controls were found to be statistically identical. The findings suggest that the mdg mutation does not have a primary or direct effect on CPK activity. 相似文献