全文获取类型
收费全文 | 2971篇 |
免费 | 231篇 |
国内免费 | 2篇 |
专业分类
3204篇 |
出版年
2022年 | 48篇 |
2021年 | 87篇 |
2020年 | 41篇 |
2019年 | 54篇 |
2018年 | 66篇 |
2017年 | 51篇 |
2016年 | 79篇 |
2015年 | 136篇 |
2014年 | 172篇 |
2013年 | 204篇 |
2012年 | 233篇 |
2011年 | 205篇 |
2010年 | 146篇 |
2009年 | 113篇 |
2008年 | 164篇 |
2007年 | 138篇 |
2006年 | 153篇 |
2005年 | 121篇 |
2004年 | 120篇 |
2003年 | 116篇 |
2002年 | 104篇 |
2001年 | 34篇 |
2000年 | 28篇 |
1999年 | 28篇 |
1998年 | 23篇 |
1997年 | 15篇 |
1996年 | 19篇 |
1995年 | 13篇 |
1994年 | 19篇 |
1993年 | 16篇 |
1992年 | 25篇 |
1991年 | 23篇 |
1990年 | 19篇 |
1989年 | 18篇 |
1988年 | 13篇 |
1987年 | 23篇 |
1986年 | 19篇 |
1985年 | 16篇 |
1984年 | 25篇 |
1983年 | 13篇 |
1982年 | 18篇 |
1981年 | 12篇 |
1979年 | 27篇 |
1976年 | 13篇 |
1975年 | 18篇 |
1974年 | 16篇 |
1973年 | 16篇 |
1972年 | 15篇 |
1971年 | 14篇 |
1970年 | 15篇 |
排序方式: 共有3204条查询结果,搜索用时 15 毫秒
121.
Ajay Kumar Kent Eskridge David D. Jones Milford A. Hanna 《Bioresource technology》2009,100(6):2062-2068
In this study, thermochemical biomass gasification was performed on a bench-scale fluidized-bed gasifier with steam and air as fluidizing and oxidizing agents. Distillers grains, a non-fermentable byproduct of ethanol production, were used as the biomass feedstock for the gasification. The goal was to investigate the effects of furnace temperature, steam to biomass ratio and equivalence ratio on gas composition, carbon conversion efficiency and energy conversion efficiency of the product gas. The experiments were conducted using a 3 × 3 × 3 full factorial design with temperatures of 650, 750 and 850 °C, steam to biomass ratios of 0, 7.30 and 14.29 and equivalence ratios of 0.07, 0.15 and 0.29. Gasification temperature was found to be the most influential factor. Increasing the temperature resulted in increases in hydrogen and methane contents, carbon conversion and energy efficiencies. Increasing equivalence ratio decreased the hydrogen content but increased carbon conversion and energy efficiencies. The steam to biomass ratio was optimal in the intermediate levels for maximal carbon conversion and energy efficiencies. 相似文献
122.
Johansson H Nordling K Weaver TE Johansson J 《The Journal of biological chemistry》2006,281(30):21032-21039
Native lung surfactant protein C (SP-C) is a 4.2-kDa acylpeptide that associates with alveolar surfactant phospholipids via a transmembrane alpha-helix. This helix contains mainly Val, although poly-Val is inefficient in helix formation, and helical SP-C can spontaneously convert to beta-sheet aggregates and amyloid-like fibrils. SP-C is cleaved out from a 21-kDa integral membrane protein, proSP-C, in the alveolar type II cell. Recently several mutations localized in the endoplasmic reticulum-lumenal (C-terminal) part of proSP-C (CTproSP-C) have been associated with intracellular accumulation of toxic forms of proSP-C, low levels of mature SP-C, and development of interstitial lung disease. CTproSP-C contains a approximately 100-residue Brichos domain of unknown function that is also found in other membrane proteins associated with amyloid formation, dementia, and cancer. Here we find that recombinant CTproSP-C binds lipid-associated SP-C, which is in beta-strand conformation, and that this interaction results in an increased helical content. In contrast, CTproSP-C does not bind alpha-helical SP-C. Recombinant CTproSP-C(L188Q), a mutation associated with interstitial lung disease, shows secondary and quaternary structures similar to those of wild type CTproSP-C but is unable to bind lipid-associated beta-strand SP-C. Transfection of CTproSP-C into HEK293 cells that express proSP-C(L188Q) increases the amount of proSP-C protein, whereas no effect is seen on cells expressing wild type proSP-C. These findings suggest that CTproSP-C binds nonhelical SP-C and thereby prevents beta-sheet aggregation and that mutations in CTproSP-C can interfere with this function. 相似文献
123.
Brzeska H Guag J Preston GM Titus MA Korn ED 《The Journal of biological chemistry》2012,287(18):14923-14936
Class I myosins have a single heavy chain comprising an N-terminal motor domain with actin-activated ATPase activity and a C-terminal globular tail with a basic region that binds to acidic phospholipids. These myosins contribute to the formation of actin-rich protrusions such as pseudopodia, but regulation of the dynamic localization to these structures is not understood. Previously, we found that Acanthamoeba myosin IC binds to acidic phospholipids in vitro through a short sequence of basic and hydrophobic amino acids, BH site, based on the charge density of the phospholipids. The tail of Dictyostelium myosin IB (DMIB) also contains a BH site. We now report that the BH site is essential for DMIB binding to the plasma membrane and describe the molecular basis of the dynamic relocalization of DMIB in live cells. Endogenous DMIB is localized uniformly on the plasma membrane of resting cells, at active protrusions and cell-cell contacts of randomly moving cells, and at the front of motile polarized cells. The BH site is required for association of DMIB with the plasma membrane at all stages where it colocalizes with phosphoinositide bisphosphate/phosphoinositide trisphosphate (PIP(2)/PIP(3)). The charge-based specificity of the BH site allows for in vivo specificity of DMIB for PIP(2)/PIP(3) similar to the PH domain-based specificity of other class I myosins. However, DMIB-head is required for relocalization of DMIB to the front of migrating cells. Motor activity is not essential, but the actin binding site in the head is important. Thus, dynamic relocalization of DMIB is determined principally by the local PIP(2)/PIP(3) concentration in the plasma membrane and cytoplasmic F-actin. 相似文献
124.
Hanna Skubatz Michelle D. Brot Kimberly M. Stock Brian Klatt George P. Thomas 《International journal of peptide research and therapeutics》2009,15(4):293-301
The efficacy of a novel tetrapeptide sequence, FLPS (Phe-Leu-Pro-Ser), to alleviate severe pain associated with surgical incision
is demonstrated in the Brennan model, a model used for developing new drugs for postoperative pain in humans. The tetrapeptide
(100 mg/kg dose) administered by subdermal injection completely alleviated post-incisional pain in rats using the hindpaw
withdrawal as an endpoint response. When the tetrapeptide (0.15 mg/paw) was topically applied to the vicinity of the surgical
wound, it also alleviated pain. Statistically significant increases in pain threshold (assessed by von Frey filaments pressed
against the surgical wound, 15–20 min after dosing) were observed on the day of surgery and on the third day post-surgery.
Up to a 0.5°C decrease in body temperature under basal conditions and yeast-provoked pyrexia was observed at doses that alleviate
pain. The tetrapeptide does not exhibit any significant anti-edema activity in carrageenan-induced hindpaw edema, and does
not affect human recombinant cyclooxygenase-2 activity, indicating that the analgesic property of the tetrapeptide is unlikely
to be mediated through inflammatory pathways. The tetrapeptide at 10 μM, a dose that is sufficient to increase the pain threshold
in rats, does not compete with naloxone for the opioid receptors in membrane preparations from rat brain, indicating that
it does not mediate its effect through the opioid receptors. It also does not bind to the vanilloid receptor, indicating that
peripheral vanilloid receptors are not involved in pain relief by the tetrapeptide. 相似文献
125.
The fine structure of tritiated thymidine-labeled cells in antigen-stimulated mouse spleen germinal centers is described. In studies on the ultrastructural level, two labeled cell types found in germinal centers are observed. Large lymphocytes are characterized by their very numerous free ribosomes, a paucity of endoplasmic reticulum, relatively few mitochondria, and a poorly developed Golgi region. The nuclei are large and vesicular, and large nucleoli are present. A second labeled cell type appears to contain more mitochondria and has a higher development of the Golgi area. The nucleus contains large, numerous blocks of chromatin, indicative of a more differentiated cell type. Reticular cells, both phagocytic and non-phagocytic, were not observed to be labeled in the germinal centers. 相似文献
126.
Hendrik Koliwer‐Brandl Paulina Knobloch Caroline Barisch Amanda Welin Nabil Hanna Thierry Soldati Hubert Hilbi 《Cellular microbiology》2019,21(6)
The causative agent of tuberculosis, Mycobacterium tuberculosis, and its close relative Mycobacterium marinum manipulate phagocytic host cells, thereby creating a replication‐permissive compartment termed the Mycobacterium‐containing vacuole (MCV). The phosphoinositide (PI) lipid pattern is a crucial determinant of MCV formation and is targeted by mycobacterial PI phosphatases. In this study, we establish an efficient phage transduction protocol to construct defined M. marinum deletion mutants lacking one or three phosphatases, PtpA, PtpB, and/or SapM. These strains were defective for intracellular replication in macrophages and amoebae, and the growth defect was complemented by the corresponding plasmid‐borne genes. Fluorescence microscopy of M. marinum‐infected Dictyostelium discoideum revealed that MCVs harbouring mycobacteria lacking PtpA, SapM, or all three phosphatases accumulate significantly more phosphatidylinositol‐3‐phosphate (PtdIns3P) compared with MCVs containing the parental strain. Moreover, PtpA reduced MCV acidification by blocking the recruitment of the V‐ATPase, and all three phosphatases promoted bacterial escape from the pathogen vacuole to the cytoplasm. In summary, the secreted M. marinum phosphatases PtpA, PtpB, and SapM determine the MCV PI pattern, compartment acidification, and phagosomal escape. 相似文献
127.
Kirsti Hllsten Hannele Yki‐Jrvinen Pauliina Peltoniemi Vesa Oikonen Teemu Takala Jukka Kemppainen Hanna Laine Jrgen Bergman Geremia B. Bolli Juhani Knuuti Pirjo Nuutila 《Obesity (Silver Spring, Md.)》2003,11(2):257-265
Objective: Insulin resistance in obese subjects results in the impaired use of glucose by insulin‐sensitive tissues, e.g., skeletal muscle. In the present study, we determined whether insulin resistance in obesity is associated with an impaired ability of exercise to stimulate muscle blood flow, oxygen delivery, or glucose uptake. Research Methods and Procedures: Nine obese (body mass index = 36 ± 2 kg/m2) and 11 age‐matched nonobese men (body mass index = 22 ± 1 kg/m2) performed one‐legged isometric exercise during hyperinsulinemia. Rates of femoral muscle blood flow, oxygen consumption, and glucose uptake were measured simultaneously in both legs using [15O]H2O, [15O]O2, [18F]fluoro‐deoxy‐glucose, and positron emission tomography. Results: The obese subjects exhibited resistance to insulin stimulation of glucose uptake in resting muscle, regardless of whether glucose uptake was expressed per kilogram of femoral muscle mass (p = 0.001) or per the total mass of quadriceps femoris muscle. At similar workloads, oxygen consumption, blood flow, and glucose uptake were lower in the obese than the nonobese subjects when expressed per kilogram of muscle, but similar when expressed per quadriceps femoris muscle mass. Discussion: We conclude that obesity is characterized by insulin resistance of glucose uptake in resting skeletal muscle regardless of how glucose uptake is expressed. When compared with nonobese individuals at similar absolute workloads and under identical hyperinsulinemic conditions, the ability of exercise to increase muscle oxygen uptake, blood flow, and glucose uptake per muscle mass is blunted in obese insulin‐resistant subjects. However, these defects are compensated for by an increase in muscle mass. 相似文献
128.
Turunen P Jalkanen J Heikura T Puhakka H Karppi J Nyyssönen K Ylä-Herttuala S 《Journal of lipid research》2004,45(9):1633-1639
Oxidation of LDL generates biologically active platelet-activating factor (PAF)-like phospholipid derivatives, which have potent proinflammatory activity. These products are inactivated by lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme capable of hydrolyzing PAF-like phospholipids. In this study, we generated an adenovirus (Ad) encoding human Lp-PLA2 and injected 10(8), 10(9), and 10(10) plaque-forming unit doses of Adlp-PLA2 and control AdlacZ intra-arterially into rabbits to achieve overexpression of Lp-PLA2 in liver and in vivo production of Lp-PLA2-enriched LDL. As a result, LDL particles with 3-fold increased Lp-PLA2 activity were produced with the highest virus dose. Increased Lp-PLA2 activity in LDL particles decreased the degradation rate in RAW 264 macrophages after standard in vitro oxidation to 60-80% compared with LDL isolated from LacZ-transduced control rabbits. The decrease was proportional to the virus dose and Lp-PLA2 activity. Lipid accumulation and foam cell formation in RAW 264 macrophages were also decreased when incubated with oxidized LDL containing the highest Lp-PLA2 activity. Inhibition of the Lp-PLA2 activity in the LDL particles led to an increase in lipid accumulation and foam cell formation. It is concluded that increased Lp-PLA2 activity in LDL attenuates foam cell formation and decreases LDL oxidation and subsequent degradation in macrophages. 相似文献
129.
Hanna E Ng KF MacRae IJ Bley CJ Fisher AJ Segel IH 《The Journal of biological chemistry》2004,279(6):4415-4424
ATP sulfurylase from Penicillium chrysogenum is a homohexameric enzyme that is subject to allosteric inhibition by 3'-phosphoadenosine 5'-phosphosulfate. In contrast to the wild type enzyme, recombinant ATP sulfurylase lacking the C-terminal allosteric domain was monomeric and noncooperative. All kcat values were decreased (the adenosine 5'-phosphosulfate (adenylylsulfate) (APS) synthesis reaction to 17% of the wild type value). Additionally, the Michaelis constants for MgATP and sulfate (or molybdate), the dissociation constant of E.APS, and the monovalent oxyanion dissociation constants of dead end E.MgATP.oxyanion complexes were all increased. APS release (the k6 step) was rate-limiting in the wild type enzyme. Without the C-terminal domain, the composite k5 step (isomerization of the central complex and MgPPi release) became rate-limiting. The cumulative results indicate that besides (a) serving as a receptor for the allosteric inhibitor, the C-terminal domain (b) stabilizes the hexameric structure and indirectly, individual subunits. Additionally, (c) the domain interacts with and perfects the catalytic site such that one or more steps following the formation of the binary E.MgATP and E.SO4(2-) complexes and preceding the release of MgPPi are optimized. The more negative entropy of activation of the truncated enzyme for APS synthesis is consistent with a role of the C-terminal domain in promoting the effective orientation of MgATP and sulfate at the active site. 相似文献
130.