全文获取类型
收费全文 | 2373篇 |
免费 | 212篇 |
国内免费 | 5篇 |
出版年
2022年 | 19篇 |
2021年 | 37篇 |
2020年 | 19篇 |
2019年 | 23篇 |
2018年 | 38篇 |
2017年 | 25篇 |
2016年 | 57篇 |
2015年 | 115篇 |
2014年 | 122篇 |
2013年 | 139篇 |
2012年 | 210篇 |
2011年 | 155篇 |
2010年 | 96篇 |
2009年 | 80篇 |
2008年 | 116篇 |
2007年 | 116篇 |
2006年 | 127篇 |
2005年 | 93篇 |
2004年 | 97篇 |
2003年 | 87篇 |
2002年 | 66篇 |
2001年 | 73篇 |
2000年 | 59篇 |
1999年 | 73篇 |
1998年 | 28篇 |
1997年 | 22篇 |
1996年 | 12篇 |
1995年 | 13篇 |
1994年 | 19篇 |
1993年 | 15篇 |
1992年 | 34篇 |
1991年 | 38篇 |
1990年 | 31篇 |
1989年 | 20篇 |
1988年 | 21篇 |
1987年 | 20篇 |
1986年 | 26篇 |
1985年 | 26篇 |
1984年 | 13篇 |
1983年 | 19篇 |
1982年 | 19篇 |
1981年 | 14篇 |
1980年 | 16篇 |
1979年 | 20篇 |
1978年 | 18篇 |
1976年 | 17篇 |
1975年 | 15篇 |
1974年 | 11篇 |
1973年 | 15篇 |
1972年 | 13篇 |
排序方式: 共有2590条查询结果,搜索用时 15 毫秒
171.
Due to the sensitivity of biological sample to the radiation damage, the low dose imaging conditions used for electron microscopy result in extremely noisy images. The processes of digitization, image alignment, and 3D reconstruction also introduce additional sources of noise in the final 3D structure. In this paper, we investigate the effectiveness of a bilateral denoising filter in various biological electron microscopy applications. In contrast to the conventional low pass filters, which inevitably smooth out both noise and structural features simultaneously, we found that bilateral filter holds a distinct advantage in being capable of effectively suppressing noise without blurring the high resolution details. In as much, we have applied this technique to individual micrographs, entire 3D reconstructions, segmented proteins, and tomographic reconstructions. 相似文献
172.
Chiu LZ Fry AC Weiss LW Schilling BK Brown LE Smith SL 《Journal of strength and conditioning research / National Strength & Conditioning Association》2003,17(4):671-677
To determine if training status directly impacted the response to postactivation potentiation, athletes in sports requiring explosive strength (ATH; n = 7) were compared to recreationally trained (RT; n = 17) individuals. Over the course of 4 sessions, subjects performed rebound and concentric-only jump squats with 30%, 50%, and 70% 1 RM loads. Jump squats were performed 5 minutes and 18.5 minutes following control or heavy load warm-ups. Heavy load warm-up consisted of 5 sets of 1 repetition at 90% 1 RM back squat. Jump squat performance was assessed with a force platform and position transducer. Heavy load warm-up did not have an effect on the subjects as a single sample. However, when percent potentiation was compared between ATH and RT groups, force and power parameters were significantly greater for ATH (p < 0.05). Postactivation potentiation may be a viable method of acutely enhancing explosive strength performance in athletic but not recreationally trained individuals. Reference Data: Chiu, L.Z.F., A.C. Fry, L.W. Weiss, B.K. Schilling, L.E. Brown, and S.L. Smith. Postactivation potentiation response in athletic and recreationally trained individuals. 相似文献
173.
PKD in intestinal epithelial cells: rapid activation by phorbol esters, LPA, and angiotensin through PKC 总被引:3,自引:0,他引:3
Protein kinase C (PKC) isimplicated in the regulation of multiple important functions inintestinal epithelial cells, but the downstream signaling targets ofPKCs in these cells remain poorly characterized. Here we report thattreatment of normal rat intestinal cell lines IEC-6 and IEC-18 withphorbol 12,13-dibutyrate (PDBu) led to a rapid and strikingPKC-dependent activation of protein kinase D (PKD; also known asPKCµ). Unlike conventional and novel PKCs, PKD did not undergodownregulation in response to prolonged (24 h) exposure of IEC-6 orIEC-18 cells to PDBu. PKD was also rapidly activated in these cells bylysophosphatidic acid (LPA) or angiotensin in a concentration-dependentfashion via a PKC-dependent pathway. EC50 values were 0.1 µM and 2 nM for LPA and angiotensin II, respectively. LPA-induced PKDactivation was prevented selectively by treatment with pertussis toxin.PKD activation was tightly associated with an increase in PKDautophosphorylation at serine 916. Our results identify PKD as a novelearly point of convergence and integration of Gi andGq signaling in intestinal epithelial cells. 相似文献
174.
The diffusion gradient chamber (DGC) is a novel device developed to study the response of chemotactic bacteria to combinations
of nutrients and attractants [7]. Its purpose is to characterize genetic variants that occur in many biological experiments.
In this paper, a mathematical model which describes the spatial distribution of a bacterial population within the DGC is developed.
Mathematical analysis of the model concerning positivity and boundedness of the solutions are given. An ADI (Alternating Direction
Implicit) method is constructed for finding numerical solutions of the model and carrying out computer simulations. The numerical
results of the model successfully reproduced the patterns that were observed in the experiments using the DGC.
Received: 3 June 1997 / Revised version: 15 August 2000 / Published online: 20 December 2000 相似文献
175.
Hsieh M Chiu MH Lin YH Lin CH Lu TM Li SY Li C 《Proceedings of the National Science Council, Republic of China. Part B, Life sciences》2000,24(2):76-80
Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder with expansion of trinucleotide CAG repeats in the coding region of the gene. Expansion of the repeat tract beyond the normal range produces gene products with extended polyglutamine tracts. In this study, we analyzed the distribution of the CAG repeats in the DRPLA alleles in a normal Taiwanese population. We observed 15 different alleles and found that the range of the CAG repeat number was from 7-21. The most frequent allele contained 15 CAG repeats that represented 20% of the total analyzed alleles, followed by the 17 repeats (15.8%). The heterozygosity rate of this locus was 88%. Twelve parents-to-children transmissions of the DRPLA alleles in a Machado-Joseph disease family appeared to be normal without any alteration of the CAG repeat numbers. Phenotypes of DRPLA overlapped those of autosomal dominant cerebellar ataxia (ADCA). In order to identify DRPLA patients in Taiwan, we screened six autosomal dominant cerebellar ataxia patients without expansion in known spinocerebellar ataxia genes. All six patients had the repeat numbers within the normal range; thus, the possibility of DRPLA could be excluded. 相似文献
176.
Zhou H Lin A Gu Z Chen S Park NH Chiu R 《The Journal of biological chemistry》2000,275(30):22868-22875
c-Jun N-terminal kinase (JNK) regulates gene expression in response to various extracellular stimuli. JNK can be activated by the tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA) in normal human oral keratinocytes but not in human keratinocytes that have been immortalized (HOK-16B and HaCaT) or transformed (HOK-16B-Bap-T) nor in a cervical carcinoma cell line (HeLa). The refractory JNK activation response to TPA is not due a defect in the JNK pathway, because JNK can be activated by other stimuli, e.g. UV irradiation and an alkylating agent N-methyl-N'-nitrosoguanidine in these immortalized or transformed cells. More importantly, the refractory JNK and JNKK activation response to TPA can be restored by treatment of the cells with a combination of TPA and a protein-tyrosine phosphatase inhibitor, sodium orthovanadate. Furthermore, pretreatment of cells with TPA partially inhibited UV- or N-methyl-N'-nitrosoguanidine-induced JNK activity. These results suggest that a TPA-inducible, orthovanadate-sensitive protein-tyrosine phosphatase may specifically down-regulate JNK signaling pathway in these immortalized/transformed epithelial cells. In contrast, ERK and p38/Mpk2 are not regulated by this TPA-induced phosphatase. This putative protein-tyrosine phosphatase appears to be JNK pathway-specific. 相似文献
177.
TNF-alpha induced a dose- and time-dependent increase in cyclooxygenase-2 (COX-2) expression and PGE2 formation in human NCI-H292 epithelial cells. Immunofluorescence staining demonstrated that COX-2 was expressed in cytosol and nuclear envelope. Tyrosine kinase inhibitors (genistein or herbimycin) or phosphoinositide-specific phospholipase C inhibitor (U73122) blocked TNF-alpha-induced COX-2 expression. TNF-alpha also stimulated phosphatidylinositol hydrolysis and protein kinase C (PKC) activity, and both were abolished by genistein or U73122. The PKC inhibitor, staurosporine, also inhibited TNF-alpha-induced response. The 12-O-tetradecanoylphorbol 13-acetate (TPA), a PKC activator, also stimulated COX-2 expression, this effect being inhibited by genistein or herbimycin. NF-kappaB DNA-protein binding and COX-2 promoter activity were enhanced by TNF-alpha, and these effects were inhibited by genistein, U73122, staurosporine, or pyrolidine dithiocarbamate. TPA stimulated both NF-kappaB DNA-protein binding and COX-2 promoter activity, these effects being inhibited by genistein, herbimycin, or pyrolidine dithiocarbamate. The TNF-alpha-induced, but not the TPA-induced, COX-2 promoter activity was inhibited by phospholipase C-gamma2 mutants, and the COX-2 promoter activity induced by either agent was attenuated by dominant-negative mutants of PKC-alpha, NF-kappaB-inducing kinase, or I-kappaB (inhibitory protein that dissociates from NF-kappaB) kinase (IKK)1 or 2. IKK activity was stimulated by both TNF-alpha and TPA, and these effects were inhibited by staurosporine or herbimycin. These results suggest that, in NCI-H292 epithelial cells, TNF-alpha might activate phospholipase C-gamma2 via an upstream tyrosine kinase to induce activation of PKC-alpha and protein tyrosine kinase, resulting in the activation of NF-kappaB-inducing kinase and IKK1/2, and NF-kappaB in the COX-2 promoter, then initiation of COX-2 expression and PGE2 release. 相似文献
178.
The C-terminal carbohydrate-binding module (CBM17) from Clostridium cellulovorans cellulase 5A is a beta-1,4-glucan binding module with a preference for soluble chains. CBM17 binds to phosphoric acid swollen Avicel (PASA) and Avicel with association constants of 2.9 (+/-0.2) x 10(5) and 1.6 (+/-0.2) x 10(5) M(-1), respectively. The capacity values for PASA and Avicel were 11.9 and 0.4 micromol/g of cellulose, respectively. CBM17 did not bind to crystalline cellulose. CBM17 bound tightly to soluble barley beta-glucan and the derivatized celluloses HEC, EHEC, and CMC. The association constants for binding to barley beta-glucan, HEC, and EHEC were approximately 2.0 x 10(5) M(-1). Significant binding affinities were found for cello-oligosaccharides greater than three glucose units in length. The affinities for cellotriose, cellotetraose, cellopentaose, and cellohexaose were 1.2 (+/-0.3) x 10(3), 4.3 (+/-0.4) x 10(3), 3.8 (+/-0.1) x 10(4), and 1.5 (+/-0.0) x 10(5) M(-1), respectively. Fluorescence quenching studies and N-bromosuccinimide modification indicate the participation of tryptophan residues in ligand binding. The possible architecture of the ligand-binding site is discussed in terms of its binding specificity, affinity, and the participation of tryptophan residues. 相似文献
179.
Complex sounds, including human speech, contain time-varying signals like frequency modulation (FM) and amplitude modulation (AM) components. In spite of various attempts to characterize their neuronal coding in the mammalian auditory systems, a unified view of their responses has not been reached. We compared FM and AM coding in terms of receptive space with reference to the input-output relationship of the underlying neural circuits. Using extracellular recording, single unit responses to a novel stimulus (i.e. random AM or FM tone) were obtained at the auditory midbrain of the anesthetized rat. Responses could be classified into three general types, corresponding to selective sensitivity to one of the following aspects of the modulation: (a) steady state, (b) dynamic state, or (c) steady-and-dynamic states. Such response typing was basically similar between FM and AM stimuli. Furthermore, the receptive space of each unit could be characterized in a three-dimensional Cartesian co-ordinate system formed by three modulation parameters: velocity, range and intensity. This representation applies to both FM and AM responses. We concluded that the FM and AM codings are very similar at the auditory midbrain and may likely involve similar neural mechanisms. 相似文献
180.
Mass spectrometry of single-stranded restriction fragments captured by an undigested complementary sequence 总被引:1,自引:1,他引:0
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In this report, we describe a simple and accurate method to analyze restriction fragments using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The two complementary strands of restriction fragments are separated through hybridization to a capture probe, which is a single-stranded undigested fragment. Using the biotin–streptavidin linkage, the hybrid is immobilized on streptavidin-coated magnetic beads. After conditioning the captured restriction fragments, they are eluted from the probe and their molecular weights are determined. The proposed method greatly improves the quality, and reduces the complexity of the mass spectrum by analyzing only one of the complementary strands of restriction fragments. 相似文献