全文获取类型
收费全文 | 14772篇 |
免费 | 1270篇 |
国内免费 | 7篇 |
专业分类
16049篇 |
出版年
2022年 | 92篇 |
2021年 | 181篇 |
2020年 | 97篇 |
2019年 | 159篇 |
2018年 | 147篇 |
2017年 | 134篇 |
2016年 | 296篇 |
2015年 | 486篇 |
2014年 | 545篇 |
2013年 | 772篇 |
2012年 | 884篇 |
2011年 | 919篇 |
2010年 | 569篇 |
2009年 | 552篇 |
2008年 | 795篇 |
2007年 | 789篇 |
2006年 | 682篇 |
2005年 | 748篇 |
2004年 | 729篇 |
2003年 | 650篇 |
2002年 | 648篇 |
2001年 | 159篇 |
2000年 | 138篇 |
1999年 | 160篇 |
1998年 | 189篇 |
1997年 | 128篇 |
1996年 | 115篇 |
1995年 | 106篇 |
1994年 | 105篇 |
1993年 | 107篇 |
1992年 | 153篇 |
1991年 | 121篇 |
1990年 | 116篇 |
1989年 | 116篇 |
1988年 | 111篇 |
1987年 | 128篇 |
1986年 | 114篇 |
1985年 | 109篇 |
1984年 | 150篇 |
1983年 | 128篇 |
1982年 | 154篇 |
1981年 | 145篇 |
1980年 | 162篇 |
1979年 | 143篇 |
1978年 | 128篇 |
1977年 | 124篇 |
1976年 | 99篇 |
1975年 | 94篇 |
1974年 | 100篇 |
1973年 | 92篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
J.C. Kuo Edward S. Yeung 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1982,229(2)
A separation and detection scheme is presented for the determination of free, esterified and total cholesterol in human serum. Separation is accomplished by reversed-phase high-performance liquid chromatography and the eluate is monitored by the laser-based optical activity detector. The method is simple, accurate and has the advantage of specificity and selectivity when compared with the many methods commonly used. 相似文献
12.
Abstract In Trichodesmium contortum , nitrogenase was detected in only a limited number (about 10%) of microscopically distinguishable, consecutively arranged cells in central regions of the trichomes. Cells with nitrogenase also contained the photosystem II associated pigment phycoerythrin. These cells were not distinguishable from other cells on a structural basis, but were clearly visible at low magnification microscopy as all in the zone were more compact and shorter than those on either side. The compartmentalisation of nitrogenase into a chain of cells and in a possibly photosynthetic environment represents a previously undescribed phenomenon. The nitrogenase containing cells apparently perform the O2 protective function of heterocysts yet are different in several aspects. 相似文献
13.
Chien-Jung Huang Laurent Schild Edward G. Moczydlowski 《The Journal of general physiology》2012,140(4):435-454
Voltage-gated Na+ channels (NaV channels) are specifically blocked by guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar to micromolar affinity depending on key amino acid substitutions in the outer vestibule of the channel that vary with NaV gene isoforms. All NaV channels that have been studied exhibit a use-dependent enhancement of TTX/STX affinity when the channel is stimulated with brief repetitive voltage depolarizations from a hyperpolarized starting voltage. Two models have been proposed to explain the mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A, and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic selectivity and Ca2+ permeability to test the trapped ion mechanism, which attributes use-dependent enhancement of toxin affinity to electrostatic repulsion between the bound toxin and Ca2+ or Na+ ions trapped inside the channel vestibule in the closed state. Our results indicate that TTX/STX use dependence is not relieved by mutations that enhance Ca2+ permeability, suggesting that ion–toxin repulsion is not the primary factor that determines use dependence. Evidence now favors the idea that TTX/STX use dependence arises from conformational coupling of the voltage sensor domain or domains with residues in the toxin-binding site that are also involved in slow inactivation. 相似文献
14.
OBJECTIVE--To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN--Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING--Nottingham. SUBJECTS--147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES--Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS--Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS--These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia. 相似文献
15.
Peter M. Zygmunt Anna Ermund Pouya Movahed David A. Andersson Charlotte Simonsen Bo A. G. J?nsson Anders Blomgren Bryndis Birnir Stuart Bevan Alain Eschalier Christophe Mallet Ana Gomis Edward D. H?gest?tt 《PloS one》2013,8(12)
Phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate generates diacylglycerol, inositol 1,4,5-trisphosphate and protons, all of which can regulate TRPV1 activity via different mechanisms. Here we explored the possibility that the diacylglycerol metabolites 2-arachidonoylglycerol and 1-arachidonoylglycerol, and not metabolites of these monoacylglycerols, activate TRPV1 and contribute to this signaling cascade. 2-Arachidonoylglycerol and 1-arachidonoylglycerol activated native TRPV1 on vascular sensory nerve fibers and heterologously expressed TRPV1 in whole cells and inside-out membrane patches. The monoacylglycerol lipase inhibitors methylarachidonoyl-fluorophosphonate and JZL184 prevented the metabolism of deuterium-labeled 2-arachidonoylglycerol and deuterium-labeled 1-arachidonoylglycerol in arterial homogenates, and enhanced TRPV1-mediated vasodilator responses to both monoacylglycerols. In mesenteric arteries from TRPV1 knock-out mice, vasodilator responses to 2-arachidonoylglycerol were minor. Bradykinin and adenosine triphosphate, ligands of phospholipase C-coupled membrane receptors, increased the content of 2-arachidonoylglycerol in dorsal root ganglia. In HEK293 cells expressing the phospholipase C-coupled histamine H1 receptor, exposure to histamine stimulated the formation of 2-AG, and this effect was augmented in the presence of JZL184. These effects were prevented by the diacylglycerol lipase inhibitor tetrahydrolipstatin. Histamine induced large whole cell currents in HEK293 cells co-expressing TRPV1 and the histamine H1 receptor, and the TRPV1 antagonist capsazepine abolished these currents. JZL184 increased the histamine-induced currents and tetrahydrolipstatin prevented this effect. The calcineurin inhibitor ciclosporin and the endogenous “entourage” compound palmitoylethanolamide potentiated the vasodilator response to 2-arachidonoylglycerol, disclosing TRPV1 activation of this monoacylglycerol at nanomolar concentrations. Furthermore, intracerebroventricular injection of JZL184 produced TRPV1-dependent antinociception in the mouse formalin test. Our results show that intact 2-arachidonoylglycerol and 1-arachidonoylglycerol are endogenous TRPV1 activators, contributing to phospholipase C-dependent TRPV1 channel activation and TRPV1-mediated antinociceptive signaling in the brain. 相似文献
16.
Rachel M. Haywood Andrew W. D. Claxson Geoffrey E. Hawkes David P. Richardson Declan P. Naughton Gregory Coumbarides Jane Hawkes Edward J. Lynch Martin C. Grootveld 《Free radical research》1995,22(5):441-482
High field (400 and 600 MHz) proton NMR spectroscopy has been employed to investigate the thermally-induced autoxidation of glycerol-bound polyunsaturated fatty acids present in intact culinary frying oils and fats. Heating of these materials at 180°C for periods of 30, 60 and 90 min. generated a variety of peroxidation products, notably aldehydes (alkanals, trans-2-alkenals and alka-2, 4-dienals) and their conjugated hydroperoxydiene precursors. Since such aldehydes appear to be absorbed into the systemic circulation from the gut in vivo, the toxicological significance of their production during standard frying practices is discussed. 相似文献
17.
Locusts jump by rapidly releasing energy from cuticular springs built into the hind femur that deform when the femur muscle contracts. This study is the first to examine the effect of temperature on jump energy at each life stage of any orthopteran. Ballistics and high-speed cinematography were used to quantify the energy, distance, and take-off angle of the jump at 15, 25, and 35°C in the locust Locusta migratoria. Allometric analysis across the five juvenile stages at 35°C reveals that jump distance (D; m) scales with body mass (M; g) according to the power equation D = 0.35M
0.17±0.08 (95% CI), jump take-off angle (A; degrees) scales as A = 52.5M
0.00±0.06, and jump energy (E; mJ per jump) scales as E = 1.91M
1.14±0.09. Temperature has no significant effect on the exponent of these relationships, and only a modest effect on the elevation, with an overall Q10 of 1.08 for jump distance and 1.09 for jump energy. On average, adults jump 87% farther and with 74% more energy than predicted based on juvenile scaling data. The positive allometric scaling of jump distance and jump energy across the juvenile life stages is likely facilitated by the concomitant relative increase in the total length (L
f+t; mm) of the femur and tibia of the hind leg, L
f+t = 34.9M
0.37±0.02. The weak temperature-dependence of jump performance can be traced to the maximum tension of the hind femur muscle and the energy storage capacity of the femur''s cuticular springs. The disproportionately greater jump energy and jump distance of adults is associated with relatively longer (12%) legs and a relatively larger (11%) femur muscle cross-sectional area, which could allow more strain loading into the femur''s cuticular springs. Augmented jump performance in volant adult locusts achieves the take-off velocity required to initiate flight. 相似文献
18.
Strategies for signal amplification in nucleic acid detection 总被引:3,自引:0,他引:3
S. Calin Andras J. Brian Power Edward C. Cocking Michael R. Davey 《Molecular biotechnology》2001,19(1):29-44
Many aspects of molecular genetics necessitate the detection of nucleic acid sequences. Current approaches involving target
amplification (in situ PCR, Primed in situ Labeling, Self-Sustained Sequence Replication, Strand Displacement Amplification), probe amplification (Ligase Chain Reaction,
Padlock Probes, Rolling Circle Amplification) and signal amplification (Tyramide Signal Amplification, Branched DNA Amplification)
are summarized in the present review, together with their advantages and limitations. 相似文献
19.
20.
Tristan J. Iseli Nigel Turner Xiao-Yi Zeng Gregory J. Cooney Edward W. Kraegen Sheng Yao Yang Ye David E. James Ji-Ming Ye 《PloS one》2013,8(4)
We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKKβ inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK. 相似文献