全文获取类型
收费全文 | 1601篇 |
免费 | 137篇 |
国内免费 | 2篇 |
出版年
2022年 | 11篇 |
2021年 | 35篇 |
2020年 | 15篇 |
2019年 | 22篇 |
2018年 | 31篇 |
2017年 | 28篇 |
2016年 | 40篇 |
2015年 | 69篇 |
2014年 | 79篇 |
2013年 | 98篇 |
2012年 | 121篇 |
2011年 | 111篇 |
2010年 | 69篇 |
2009年 | 62篇 |
2008年 | 86篇 |
2007年 | 90篇 |
2006年 | 80篇 |
2005年 | 70篇 |
2004年 | 73篇 |
2003年 | 72篇 |
2002年 | 71篇 |
2001年 | 11篇 |
2000年 | 13篇 |
1999年 | 17篇 |
1998年 | 23篇 |
1997年 | 12篇 |
1996年 | 11篇 |
1995年 | 14篇 |
1994年 | 8篇 |
1993年 | 16篇 |
1992年 | 14篇 |
1991年 | 10篇 |
1990年 | 11篇 |
1989年 | 7篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 14篇 |
1983年 | 18篇 |
1982年 | 13篇 |
1981年 | 10篇 |
1980年 | 17篇 |
1978年 | 7篇 |
1977年 | 10篇 |
1976年 | 10篇 |
1974年 | 7篇 |
1968年 | 5篇 |
1964年 | 6篇 |
1960年 | 5篇 |
排序方式: 共有1740条查询结果,搜索用时 15 毫秒
171.
Proteomic analysis of Brucella abortus cell envelope and identification of immunogenic candidate proteins for vaccine development 总被引:1,自引:0,他引:1
Connolly JP Comerci D Alefantis TG Walz A Quan M Chafin R Grewal P Mujer CV Ugalde RA DelVecchio VG 《Proteomics》2006,6(13):3767-3780
Brucella abortus is the etiologic agent of bovine brucellosis and causes a chronic disease in humans known as undulant fever. In livestock the disease is characterized by abortion and sterility. Live, attenuated vaccines such as S19 and RB51 have been used to control the spread of the disease in animals; however, they are considered unsafe for human use and they induce abortion in pregnant cattle. For the development of a safer and equally efficacious vaccine, immunoproteomics was utilized to identify novel candidate proteins from B. abortus cell envelope (CE). A total of 163 proteins were identified using 2-DE with MALDI-TOF MS and LC-MS/MS. Some of the major protein components include outer-membrane protein (OMP) 25, OMP31, Omp2b porin, and 60 kDa chaperonin GroEL. 2-DE Western blot analyses probed with antiserum from bovine and a human patient infected with Brucella identified several new immunogenic proteins such as fumarate reductase flavoprotein subunit, F0F1-type ATP synthase alpha subunit, and cysteine synthase A. The elucidation of the immunome of B. abortus CE identified a number of candidate proteins for developing vaccines against Brucella infection in bovine and humans. 相似文献
172.
Andrzej Bielecki Piotr Kalita Marian Lewandowski Bartłomiej Siwek 《Biological cybernetics》2010,102(6):489-502
Neurotransmitters in the terminal bouton of a presynaptic neuron are stored in vesicles, which diffuse in the cytoplasm and,
after a stimulation signal is received, fuse with the membrane and release its contents into the synaptic cleft. It is commonly
assumed that vesicles belong to three pools whose content is gradually exploited during the stimulation. This article presents
a model that relies on the assumption that the release ability is associated with the vesicle location in the bouton. As a
modeling tool, partial differential equations are chosen as they allow one to express the continuous dependence of the unknown
vesicle concentration on both the time and space variables. The model represents the synthesis, concentration-gradient-driven
diffusion, and accumulation of vesicles as well as the release of neuroactive substances into the cleft. An initial and boundary
value problem is numerically solved using the finite element method (FEM) and the simulation results are presented and discussed.
Simulations were run for various assumptions concerning the parameters that govern the synthesis and diffusion processes.
The obtained results are shown to be consistent with those obtained for a compartment model based on ordinary differential
equations. Such studies can be helpful in gaining a deeper understanding of synaptic processes including physiological pathologies.
Furthermore, such mathematical models can be useful for estimating the biological parameters that are included in a model
and are hard or impossible to measure directly. 相似文献
173.
The ultrastructure of spermatozoa of the acotylean Phaenocelis peleca and the cotylean Boninia divae is described. All spermatozoa are filiform and biflagellate with a 9+"1" microtubular pattern in the axoneme. Sperm characters
in P. peleca follow the morphologies described for other acotyleans, with axonemes exiting the sperm shaft at the distal end and remaining
in close contact with the sperm membrane. The nucleus occupies the proximal region of the shaft, and two types of dense bodies
and mitochondria are located at the distal end. Unlike other members of the Cotylea, the axonemes of B. divae spermatozoa are incorporated into the sperm shaft, leaving the shaft at some distance from the distal end and then remaining
free. This type of morphology is characteristic for acotyleans. Additionally, the spermatozoa of B. divae contain only one type of dense bodies plus a unique structure, which we call a central core. The nucleus in this species
is unique as well; it shows periodic constrictions and rings of electron-dense granules, characters that further contribute
to the distinct status of Boniniidae. 相似文献
174.
175.
176.
Rafii MS Hagiwara H Mercado ML Seo NS Xu T Dugan T Owens RT Hook M McQuillan DJ Young MF Fallon JR 《Journal of cellular physiology》2006,209(2):439-447
The dystrophin-associated protein complex (DAPC), which links the cytoskeleton to the extracellular matrix, is essential for muscle cell survival, and is defective in a wide range of muscular dystrophies. The DAPC contains two transmembrane subcomplexes-the dystroglycans and the sarcoglycans. Although several extracellular binding partners have been identified for the dystroglycans, none have been described for the sarcoglycan subcomplex. Here we show that the small leucine-rich repeat (LRR) proteoglycan biglycan binds to alpha- and gamma-sarcoglycan as judged by ligand blot overlay and co-immunoprecipitation assays. Our studies with biglycan-decorin chimeras show that alpha- and gamma-sarcoglycan bind to distinct sites on the polypeptide core of biglycan. Both biglycan proteoglycan as well as biglycan polypeptide lacking glycosaminoglycan (GAG) side chains are components of the dystrophin glycoprotein complex isolated from adult skeletal muscle membranes. Finally, our immunohistochemical and biochemical studies with biglycan null mice show that the expression of alpha- and gamma-sarcoglycan is selectively reduced in muscle from young (P14-P21) animals, while levels in adult muscle (> or = P35) are unchanged. We conclude that biglycan is a ligand for two members of the sarcoglycan complex and regulates their expression at discrete developmental ages. 相似文献
177.
Michel Goldberg Dominique Septier Ake Oldberg Marian F Young Laurent G Ameye 《The journal of histochemistry and cytochemistry》2006,54(5):525-537
To determine the functions of fibromodulin (Fmod), a small leucine-rich keratan sulfate proteoglycan in tooth formation, we investigated the distribution of Fmod in dental tissues by immunohistochemistry and characterized the dental phenotype of 1-day-old Fmod-deficient mice using light and transmission electron microscopy. Immunohistochemistry was also used to compare the relative protein expression of dentin sialoprotein (DSP), dentin matrix protein-1 (DMP 1), bone sialoprotein (BSP), and osteopontin (OPN) between Fmod-deficient mice and wild-type mice. In normal mice and rats, Fmod immunostaining was mostly detected in the distal cell bodies of odontoblasts and in the stratum intermedium and was weaker in odontoblast processes and predentin. The absence of Fmod impaired dentin mineralization, increased the diameter of the collagen fibrils throughout the whole predentin, and delayed enamel formation. Immunohistochemistry provides evidence for compensatory mechanisms in Fmod-deficient mice. Staining for DSP and OPN was decreased in molars, whereas DMP 1 and BSP were enhanced. In the incisors, labeling for DSP, DMP 1, and BSP was strongly increased in the pulp and odontoblasts, whereas OPN staining was decreased. Positive staining was also seen for DMP 1 and BSP in secretory ameloblasts. Together these studies indicate that Fmod restricts collagen fibrillogenesis in predentin while promoting dentin mineralization and the early stages of enamel formation. 相似文献
178.
Hooks JJ Chin MS Srinivasan K Momma Y Hooper LC Nagineni CN Chan CC Detrick B 《Microbes and infection / Institut Pasteur》2006,8(8):2236-2244
Cytomegalovirus (CMV) retinitis is characterized by alterations in retinal cell function and host responses to virus replication. The goal of this study was to evaluate the induction of cyclooxygenase-2 (COX-2) and prostaglandin (PGE) in CMV infected human retinal pigment epithelial (RPE) cells and to determine their effect on virus replication. CMV immediate early (IE) protein and COX-2 proteins were identified in RPE cells in retinal tissue sections from patients with CMV retinitis. COX-2 mRNA and protein were induced after CMV infection of human RPE cell cultures. CMV infection of RPE cells induced translocation of NF-kappaB from the cytoplasm to the nucleus. PGE1 and PGE2 were significantly (p<0.001) increased in human RPE cell cultures infected with CMV. Inhibition of CMV IE gene by antisense oligonucleotides abrogated induction of mRNA for COX-2 and protein synthesis of COX-2 and PGE2. PGE enhanced CMV plaque formation and real time PCR analysis revealed that PGE treatment significantly increased CMV DNA copy numbers. These studies demonstrate that when CMV replicates within human RPE cells, COX-2 induction augments virus replication via the PGE pathway. The induction of COX-2 and PGE during retinal CMV infection may augment virus replication and alter a variety of retinal physiological responses. 相似文献
179.
Wadwa RP Kinney GL Ogden L Snell-Bergeon JK Maahs DM Cornell E Tracy RP Rewers M 《The international journal of biochemistry & cell biology》2006,38(5-6):996-1003
INTRODUCTION: Soluble interleukin-2 receptor (sIL2r), a marker of T cell activation, is elevated in inflammatory processes, such as rheumatoid arthritis, hepatitis and neoplasm. We explored a potential association between plasma sIL2r levels and progression of coronary artery calcification (CAC), a marker for subclinical atherosclerosis, in a prospectively followed cohort of type 1 diabetic and non-diabetic subjects, aged 20-59 years, with no history of coronary artery disease. MATERIALS AND METHODS: CAC progression was assessed by electron beam tomography over 2.6 years (range 1.6-3.2). Plasma sIL2r levels were measured in a nested case-control substudy of 98 subjects (67 diabetic, 31 non-diabetic) with and 173 subjects (84 diabetic, 89 non-diabetic) without significant CAC progression. Log-transformed sIL2r levels were analyzed by conditional logistic regression to compare subjects with and without significant CAC progression. RESULTS: SIL2r was a significant predictor for CAC progression after adjusting for presence of baseline CAC, age, gender, diabetes status, baseline calcium volume score and adiponectin (OR 1.99, 95% CI 1.09-3.61, p = 0.02 for a doubling of sIL2r level). Addition of BMI, LDL, HDL, hypertension, smoking status, HbA1c, CRP, fibrinogen, homocysteine and PAI-1 to regression models weakened but did not remove sIL2r as a predictor of CAC progression. There was no indication that this effect was different by diabetes status (p = 0.6 for diabetes-sIL2r interaction). DISCUSSION: Elevated plasma sIL2r is associated with CAC progression independent of traditional coronary artery disease risk factors in type 1 diabetic and non-diabetic young adults. SIL2r should be considered as a novel marker of inflammation leading to coronary artery disease. 相似文献
180.