全文获取类型
收费全文 | 4755篇 |
免费 | 372篇 |
国内免费 | 1篇 |
专业分类
5128篇 |
出版年
2023年 | 25篇 |
2022年 | 64篇 |
2021年 | 119篇 |
2020年 | 51篇 |
2019年 | 73篇 |
2018年 | 96篇 |
2017年 | 85篇 |
2016年 | 147篇 |
2015年 | 260篇 |
2014年 | 243篇 |
2013年 | 328篇 |
2012年 | 417篇 |
2011年 | 395篇 |
2010年 | 247篇 |
2009年 | 194篇 |
2008年 | 306篇 |
2007年 | 298篇 |
2006年 | 263篇 |
2005年 | 257篇 |
2004年 | 243篇 |
2003年 | 218篇 |
2002年 | 237篇 |
2001年 | 42篇 |
2000年 | 34篇 |
1999年 | 47篇 |
1998年 | 52篇 |
1997年 | 45篇 |
1996年 | 19篇 |
1995年 | 35篇 |
1994年 | 31篇 |
1993年 | 34篇 |
1992年 | 25篇 |
1991年 | 14篇 |
1990年 | 16篇 |
1989年 | 18篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 15篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 17篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1976年 | 10篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1969年 | 5篇 |
排序方式: 共有5128条查询结果,搜索用时 15 毫秒
61.
MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals 总被引:14,自引:0,他引:14
Lou Z Minter-Dykhouse K Franco S Gostissa M Rivera MA Celeste A Manis JP van Deursen J Nussenzweig A Paull TT Alt FW Chen J 《Molecular cell》2006,21(2):187-200
MDC1 functions in checkpoint activation and DNA repair following DNA damage. To address the physiological role of MDC1, we disrupted the MDC1 gene in mice. MDC1-/- mice recapitulated many phenotypes of H2AX-/- mice, including growth retardation, male infertility, immune defects, chromosome instability, DNA repair defects, and radiation sensitivity. At the molecular level, H2AX, MDC1, and ATM form a positive feedback loop, with MDC1 directly mediating the interaction between H2AX and ATM. MDC1 binds phosphorylated H2AX through its BRCT domain and ATM through its FHA domain. Through these interactions, MDC1 accumulates activated ATM flanking the sites of DNA damage, facilitating further ATM-dependent phosphorylation of H2AX and the amplification of DNA damage signals. In the absence of MDC1, many downstream ATM signaling events are defective. These results suggest that MDC1, as a signal amplifier of the ATM pathway, is vital in controlling proper DNA damage response and maintaining genomic stability. 相似文献
62.
Anaerobic Bioremediation of Groundwater Containing a Mixture of 1,1,2,2-Tetrachloroethane and Chloroethenes 总被引:2,自引:0,他引:2
This study investigated the biotransformation pathways of 1,1,2,2-tetrachloroethane (1,1,2,2-TeCA) in the presence of chloroethenes
(i.e. tetrachloroethene, PCE; trichloroethene, TCE) in anaerobic microcosms constructed with subsurface soil and groundwater
from a contaminated site. When amended with yeast extract, lactate, butyrate, or H2 and acetate, 1,1,2,2-TeCA was initially dechlorinated via both hydrogenolysis to 1,1,2-trichloroethane (1,1,2-TCA) (major
pathway) and dichloroelimination to dichloroethenes (DCEs) (minor pathway), with both reactions occurring under sulfidogenic
conditions. In the presence of only H2, the hydrogenolysis of 1,1,2,2-TeCA to 1,1,2-TCA apparently required the presence of acetate to occur. Once formed, 1,1,2-TCA
was degraded predominantly via dichloroelimination to vinyl chloride (VC). Ultimately, chloroethanes were converted to chloroethenes
(mainly VC and DCEs) which persisted in the microcosms for very long periods along with PCE and TCE originally present in
the groundwater. Hydrogenolysis of chloroethenes occurred only after highly reducing methanogenic conditions were established.
However, substantial conversion to ethene (ETH) was observed only in microcosms amended with yeast extract (200 mg/l), suggesting
that groundwater lacked some nutritional factors which were likely provided to dechlorinating microorganisms by this complex
organic substrate. Bioaugmentation with an H2-utilizing PCE-dechlorinating Dehalococcoides spp. -containing culture resulted in the conversion of 1,1,2,2-TeCA, PCE and TCE to ETH and VC. No chloroethanes accumulated
during degradation suggesting that 1,1,2,2-TeCA was degraded through initial dichloroelimination into DCEs and then typical
hydrogenolysis into ETH and VC. 相似文献
63.
João Afonso Baptista Monica Truninger 《The journal of the Royal Anthropological Institute》2022,28(2):556-576
Doing research on fishery commodities in Portugal led us to an enigma: for a dead fish to be fresco (fresh) it must be alive. This paradox manifests at a popular, commercial, and legal level. It denotes the interruption of the difference between being dead and being alive in the commodity form. In Portugal, we suggest, the commercialization of peixe fresco (fresh fish) is based on the production and consumption of edible ‘zombis’: seafood corpses technologically and symbolically crafted as undead. An open concept, ‘edible zombis’ is part of an experimental vocabulary that foregrounds the productive agency of undeadness, both biological and commercial, in the seafood economic complex. It relates to the ordinary practice of necromancy in the commodity-based world. Edible zombis are commodity fetishes that fetishize their producers and consumers, suspending them from the capitalist system in which they live. 相似文献
64.
Feyisara Eyiwumi Oni Niels Geudens Joseph T. Onyeka Oluwatoyin Faith Olorunleke Ayodeji Ekundayo Salami Olumide Owolabi Omoboye Anthony Arguelles Arias Amayana Adiobo Stefaan De Neve Marc Ongena José C. Martins Monica Höfte 《Environmental microbiology》2020,22(12):5137-5155
Pseudomonas isolates from tropical environments have been underexplored and may form an untapped reservoir of interesting secondary metabolites. In this study, we compared Pseudomonas and cyclic lipopeptide (CLP) diversity in the rhizosphere of a cocoyam root rot disease (CRRD) suppressive soil in Boteva, Cameroon with those from four conducive soils in Cameroon and Nigeria. Compared with other soils, Boteva andosols were characterized by high silt, organic matter, nitrogen and calcium. Besides, the cocoyam rhizosphere at Boteva was characterized by strains belonging mainly to the P. koreensis and P. putida (sub)groups, with representations in the P. fluorescens, P. chlororaphis, P. jessenii and P. asplenii (sub)groups. In contrast, P. putida isolates were prominent in conducive soils. Regarding CLP diversity, Boteva was characterized by strains producing 11 different CLP types with cocoyamide A producers, belonging to the P. koreensis group, being the most abundant. However, putisolvin III-V producers were the most dominant in the rhizosphere of conducive soils in both Cameroon and Nigeria. Furthermore, we elucidated the chemical structure of putisolvin derivatives—putisolvin III-V, and described its biosynthetic gene cluster. We show that high Pseudomonas and metabolic diversity may be driven by microbial competition, which likely contributes to soil suppressiveness to CRRD. 相似文献
65.
Simona Tritto Giulia Gastaldi Sergey Zelenin Monica Grazioli Maria Novella Orsenigo Ulderico Ventura Umberto Laforenza Marina Zelenina 《Biochimie et biologie cellulaire》2007,85(6):675-684
Water channels AQP7 and AQP8 may be involved in transcellular water movement in the small intestine. We show that both AQP7 and AQP8 mRNA are expressed in rat small intestine. Immunoblot and immunohistochemistry experiments demonstrate that AQP7 and AQP8 proteins are present in the apical brush border membrane of intestinal epithelial cells. We investigated the effect of several metals and pH on the osmotic water permeability (Pf) of brush border membrane vesicles (BBMVs) and of AQP7 and AQP8 expressed in a cell line. Hg2+, Cu2+, and Zn2+ caused a significant decrease in the BBMV Pf, whereas Ni2+ and Li+ had no effect. AQP8-transfected cells showed a reduction in Pf in the presence of Hg2+ and Cu2+, whereas AQP7-transfected cells were insensitive to all tested metals. The Pf of both BBMVs and cells transfected with AQP7 and AQP8 was not affected by pH changes within the physiological range, and the Pf of BBMVs alone was not affected by phlorizin or amiloride. Our results indicate that AQP7 and AQP8 may play a role in water movement via the apical domain of small intestine epithelial cells. AQP8 may contribute to the water-imbalance-related clinical symptoms apparent after ingestion of high doses of Hg2+ and Cu2+. 相似文献
66.
Parthenolide sensitizes cells to X-ray-induced cell killing through inhibition of NF-kappaB and split-dose repair 总被引:2,自引:0,他引:2
Mendonca MS Chin-Sinex H Gomez-Millan J Datzman N Hardacre M Comerford K Nakshatri H Nye M Benjamin L Mehta S Patino F Sweeney C 《Radiation research》2007,168(6):689-697
Human cancers have multiple alterations in cell signaling pathways that promote resistance to cytotoxic therapy such as X rays. Parthenolide is a sesquiterpene lactone that has been shown to inhibit several pro-survival cell signaling pathways, induce apoptosis, and enhance chemotherapy-induced cell killing. We investigated whether parthenolide would enhance X-ray-induced cell killing in radiation resistant, NF-kappaB-activated CGL1 cells. Treatment with 5 microM parthenolide for 48 to 72 h inhibited constitutive NF-kappaB binding and cell growth, reduced plating efficiency, and induced apoptosis through stabilization of p53 (TP53), induction of the pro-apoptosis protein BAX, and phosphorylation of BID. Parthenolide also enhanced radiation-induced cell killing, increasing the X-ray sensitivity of CGL1 cells by a dose modification factor of 1.6. Flow cytometry revealed that parthenolide reduced the percentage of X-ray-resistant S-phase cells due to induction of p21 waf1/cip1 (CDKN1A) and the onset of G1/S and G2/M blocks, but depletion of radioresistant S-phase cells does not explain the observed X-ray sensitization. Further studies demonstrated that the enhancement of X-ray-induced cell killing by parthenolide is due to inhibition of split-dose repair. 相似文献
67.
Nishikawa K Biewener AA Aerts P Ahn AN Chiel HJ Daley MA Daniel TL Full RJ Hale ME Hedrick TL Lappin AK Nichols TR Quinn RD Satterlie RA Szymik B 《Integrative and comparative biology》2007,47(1):16-54
Neuromechanics seeks to understand how muscles, sense organs,motor pattern generators, and brain interact to produce coordinatedmovement, not only in complex terrain but also when confrontedwith unexpected perturbations. Applications of neuromechanicsinclude ameliorating human health problems (including prosthesisdesign and restoration of movement following brain or spinalcord injury), as well as the design, actuation and control ofmobile robots. In animals, coordinated movement emerges fromthe interplay among descending output from the central nervoussystem, sensory input from body and environment, muscle dynamics,and the emergent dynamics of the whole animal. The inevitablecoupling between neural information processing and the emergentmechanical behavior of animals is a central theme of neuromechanics.Fundamentally, motor control involves a series of transformationsof information, from brain and spinal cord to muscles to body,and back to brain. The control problem revolves around the specifictransfer functions that describe each transformation. The transferfunctions depend on the rules of organization and operationthat determine the dynamic behavior of each subsystem (i.e.,central processing, force generation, emergent dynamics, andsensory processing). In this review, we (1) consider the contributionsof muscles, (2) sensory processing, and (3) central networksto motor control, (4) provide examples to illustrate the interplayamong brain, muscles, sense organs and the environment in thecontrol of movement, and (5) describe advances in both roboticsand neuromechanics that have emerged from application of biologicalprinciples in robotic design. Taken together, these studiesdemonstrate that (1) intrinsic properties of muscle contributeto dynamic stability and control of movement, particularly immediatelyafter perturbations; (2) proprioceptive feedback reinforcesthese intrinsic self-stabilizing properties of muscle; (3) controlsystems must contend with inevitable time delays that can simplifyor complicate control; and (4) like most animals under a varietyof circumstances, some robots use a trial and error processto tune central feedforward control to emergent body dynamics. 相似文献
68.
69.
Christian Frkjr‐Jensen Katie S. Kindt Rex A. Kerr Hiroshi Suzuki Katya Melnik‐Martinez Beate Gerstbreih Monica Driscol William R. Schafer 《Developmental neurobiology》2006,66(10):1125-1139
Voltage‐gated calcium channels (VGCCs) serve as a critical link between electrical signaling and diverse cellular processes in neurons. We have exploited recent advances in genetically encoded calcium sensors and in culture techniques to investigate how the VGCC α1 subunit EGL‐19 and α2/δ subunit UNC‐36 affect the functional properties of C. elegans mechanosensory neurons. Using the protein‐based optical indicator cameleon, we recorded calcium transients from cultured mechanosensory neurons in response to transient depolarization. We observed that in these cultured cells, calcium transients induced by extracellular potassium were significantly reduced by a reduction‐of‐function mutation in egl‐19 and significantly reduced by L‐type calcium channel inhibitors; thus, a main source of touch neuron calcium transients appeared to be influx of extracellular calcium through L‐type channels. Transients did not depend directly on intracellular calcium stores, although a store‐independent 2‐APB and gadolinium‐sensitive calcium flux was detected. The transients were also significantly reduced by mutations in unc‐36, which encodes the main neuronal α2/δ subunit in C. elegans. Interestingly, while egl‐19 mutations resulted in similar reductions in calcium influx at all stimulus strengths, unc‐36 mutations preferentially affected responses to smaller depolarizations. These experiments suggest a central role for EGL‐19 and UNC‐36 in excitability and functional activity of the mechanosensory neurons. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 相似文献
70.
Eukaryotic cells have evolved molecular mechanisms to ensure the faithful partitioning of cellular components during cell division. The budding yeast Saccharomyces cerevisiae has to actively deliver about half of its organelles to the growing bud, while retaining the remaining organelles in the mother cell. Until lately, little was known about the inheritance of peroxisomes. Recent studies have identified the peroxisomal proteins Inp1p and Inp2p as two key regulators of peroxisome inheritance that perform antagonistic functions. Inp1p is required for the retention of peroxisomes in mother cells, whereas Inp2p promotes the bud-directed movement of these organelles. Inp1p anchors peroxisomes to the cell cortex by interacting with specific structures lining the cell periphery. On the other hand, Inp2p functions as the peroxisome-specific receptor for the class V myosin, Myo2p, thereby linking peroxisomes to the translocation machinery that propels peroxisome movement. Tight coordination between Inp1p and Inp2p ensures a fair and harmonious spatial segregation of peroxisomes upon cell division. 相似文献