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141.
Abstract We show that the classical Metropolis Monte Carlo (MMC) algorithm converges very slowly when applied to the primitive electrolyte environment for a high charge-density polyelectrolyte. This slowness of convergence, which is due to the large density inhomogeneity around the polyelectrolyte, produces noticeable errors in the ion distribution functions for MMC runs of 1.3 × 106 trial steps started from nonequilibrium distributions. We report that an algorithm which we call DSMC (for density-scaled Monte Carlo) overcomes this problem and provides relatively rapid convergence in this application. We suggest that DSMC should be well-suited for other Monte Carlo simulations on physical systems where large density inhomogeneities occur. 相似文献
142.
Abstract: Phylogenetic reconstruction of the Upper Barremian ammonite genus Gassendiceras (Gassendiceratinae) was performed using a cladistic analysis incorporating continuous data. Some morphological features were found to vary identically among all the analysed species and therefore carry no phylogenetic information (= symplesiomorphic). The single obtained cladogram allows interpreting the evolution of the Gassendiceras as an anagenetic succession of eight species, in stratigraphic order of appearance, Gassendiceras multicostatum, G. alpinum, G. hoheneggeri, G. rebouleti, G. bosellii, G. quelquejeui, G. coulletae and G. enayi. The clade Pseudoshasticrioceras/Imerites is derived from G. enayi, so the genus Gassendiceras appears to be paraphyletic. But here, we accept this fact as the best evolutive classification. The evolution over time of Gassendiceras is modulated by some processes, which could have constrained the inferred phylogenetic pattern with the drift of the global variability towards the most gracile forms over time. It is tempting to interpret this evolution as a constant selection over time of the Gassendiceras modulated by environmental control due to eustatic variation across a transgressive sequence. Thus, the most peramorphic (gracile) individuals seemed favoured at the expense of those most robust (paedomorphic). 相似文献
143.
Tatyana A. Shelkovnikova Owen M. Peters Alexey V. Deykin Natalie Connor-Robson Hannah Robinson Alexey A. Ustyugov Sergey O. Bachurin Tatyana G. Ermolkevich Igor L. Goldman Elena R. Sadchikova Elena A. Kovrazhkina Veronica I. Skvortsova Shuo-Chien Ling Sandrine Da Cruz Philippe A. Parone Vladimir L. Buchman Natalia N. Ninkina 《The Journal of biological chemistry》2013,288(35):25266-25274
Dysfunction of two structurally and functionally related proteins, FUS and TAR DNA-binding protein of 43 kDa (TDP-43), implicated in crucial steps of cellular RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and certain other neurodegenerative diseases. The proteins are intrinsically aggregate-prone and form non-amyloid inclusions in the affected nervous tissues, but the role of these proteinaceous aggregates in disease onset and progression is still uncertain. To address this question, we designed a variant of FUS, FUS 1–359, which is predominantly cytoplasmic, highly aggregate-prone, and lacks a region responsible for RNA recognition and binding. Expression of FUS 1–359 in neurons of transgenic mice, at a level lower than that of endogenous FUS, triggers FUSopathy associated with severe damage of motor neurons and their axons, neuroinflammatory reaction, and eventual loss of selective motor neuron populations. These pathological changes cause abrupt development of a severe motor phenotype at the age of 2.5–4.5 months and death of affected animals within several days of onset. The pattern of pathology in transgenic FUS 1–359 mice recapitulates several key features of human ALS with the dynamics of the disease progression compressed in line with shorter mouse lifespan. Our data indicate that neuronal FUS aggregation is sufficient to cause ALS-like phenotype in transgenic mice. 相似文献
144.
Arnab Bhattacharjee Jesper S. Oeemig Robert Kolodziejczyk Taru Meri Tommi Kajander Markus J. Lehtinen Hideo Iwa? T. Sakari Jokiranta Adrian Goldman 《The Journal of biological chemistry》2013,288(26):18685-18695
Borrelia burgdorferi spirochetes that cause Lyme borreliosis survive for a long time in human serum because they successfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is needed for this because it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis. To understand this process at the molecular level, we used a structural approach. First, we solved the solution structure of OspE by NMR, revealing a fold that has not been seen before in proteins involved in complement regulation. Next, we solved the x-ray structure of the complex between OspE and the FH C-terminal domains 19 and 20 (FH19-20) at 2.83 Å resolution. The structure shows that OspE binds FH19-20 in a way similar to, but not identical with, that used by endothelial cells to bind FH via glycosaminoglycans. The observed interaction of OspE with FH19-20 allows the full function of FH in down-regulation of complement activation on the bacteria. This reveals the molecular basis for how B. burgdorferi evades innate immunity and suggests how OspE could be used as a potential vaccine antigen. 相似文献
145.
146.
R?mulo Bertuzzi Jorge Melegati Salom?o Bueno Thaysa Ghiarone Leonardo A. Pasqua Arthur Fernandes Gáspari Adriano E. Lima-Silva Alfredo Goldman 《PloS one》2016,11(1)
Purpose
The aim of the current study is to describe the functionality of free software developed for energy system contributions and energy expenditure calculation during exercise, namely GEDAE-LaB.Methods
Eleven participants performed the following tests: 1) a maximal cycling incremental test to measure the ventilatory threshold and maximal oxygen uptake (O2max); 2) a cycling workload constant test at moderate domain (90% ventilatory threshold); 3) a cycling workload constant test at severe domain (110% O2max). Oxygen uptake and plasma lactate were measured during the tests. The contributions of the aerobic (AMET), anaerobic lactic (LAMET), and anaerobic alactic (ALMET) systems were calculated based on the oxygen uptake during exercise, the oxygen energy equivalents provided by lactate accumulation, and the fast component of excess post-exercise oxygen consumption, respectively. In order to assess the intra-investigator variation, four different investigators performed the analyses independently using GEDAE-LaB. A direct comparison with commercial software was also provided.Results
All subjects completed 10 min of exercise at moderate domain, while the time to exhaustion at severe domain was 144 ± 65 s. The AMET, LAMET, and ALMET contributions during moderate domain were about 93, 2, and 5%, respectively. The AMET, LAMET, and ALMET contributions during severe domain were about 66, 21, and 13%, respectively. No statistical differences were found between the energy system contributions and energy expenditure obtained by GEDAE-LaB and commercial software for both moderate and severe domains (P > 0.05). The ICC revealed that these estimates were highly reliable among the four investigators for both moderate and severe domains (all ICC ≥ 0.94).Conclusion
These findings suggest that GEDAE-LaB is a free software easily comprehended by users minimally familiarized with adopted procedures for calculations of energetic profile using oxygen uptake and lactate accumulation during exercise. By providing availability of the software and its source code we hope to facilitate future related research. 相似文献147.
Dyskeratosis Congenita (DC) is an inherited multisystem premature aging disorder with characteristic skin and mucosal findings as well as a predisposition to cancer and bone marrow failure. DC arises due to gene mutations associated with the telomerase complex or telomere maintenance, resulting in critically shortened telomeres. The pathogenesis of DC, as well as several congenital bone marrow failure (BMF) syndromes, converges on the DNA damage response (DDR) pathway and subsequent elevation of reactive oxygen species (ROS). Historically, DC patients have had poor outcomes following bone marrow transplantation (BMT), perhaps as a consequence of an underlying DNA hypersensitivity to cytotoxic agents. Previously, we demonstrated an activated DDR and increased ROS, augmented by chemotherapy and radiation, in somatic cells isolated from DC patients with a mutation in the RNA component of telomerase, TERC. The current study was undertaken to determine whether previous findings related to ROS and DDR in TERC patients’ cells could be extended to other DC mutations. Of particular interest was whether an antioxidant approach could counter increased ROS and decrease DC pathologies. To test this, we examined lymphocytes from DC patients from different DC mutations (TERT, TINF2, and TERC) for the presence of an active DDR and increased ROS. All DC mutations led to increased steady-state p53 (2-fold to 10-fold) and ROS (1.5-fold to 2-fold). Upon exposure to ionizing radiation (XRT), DC cells increased in both DDR and ROS to a significant degree. Exposing DC cells to hydrogen peroxide also revealed that DC cells maintain a significant oxidant burden compared to controls (1.5-fold to 3-fold). DC cell culture supplemented with N-acetylcysteine, or alternatively grown in low oxygen, afforded significant proliferative benefits (proliferation: maximum 2-fold increase; NAC: 5-fold p53 decrease; low oxygen: maximum 3.5-fold p53 decrease). Together, our data supports a mechanism whereby telomerase deficiency and subsequent shortened telomeres initiate a DDR and create a pro-oxidant environment, especially in cells carrying the TINF2 mutations. Finally, the ameliorative effects of antioxidants in vitro suggest this could translate to therapeutic benefits in DC patients. 相似文献
148.
Jelena Petrovic Yeqiao Zhou Maria Fasolino Naomi Goldman Gregory W. Schwartz Maxwell R. Mumbach Son C. Nguyen Kelly S. Rome Yogev Sela Zachary Zapataro Stephen C. Blacklow Michael J. Kruhlak Junwei Shi Jon C. Aster Eric F. Joyce Shawn C. Little Golnaz Vahedi Warren S. Pear Robert B. Faryabi 《Molecular cell》2019,73(6):1174-1190.e12
149.
Chou YH Flitney FW Chang L Mendez M Grin B Goldman RD 《Experimental cell research》2007,313(10):2236-2243
Intermediate filament (IF) proteins exist in multiple structural forms within cells including mature IF, short filaments or 'squiggles', and non-filamentous precursors called particles. These forms are interconvertible and their relative abundance is IF type, cell type- and cell cycle stage-dependent. These structures are often associated with molecular motors, such as kinesin and dynein, and are therefore capable of translocating through the cytoplasm along microtubules. The assembly of mature IF from their precursor particles is also coupled to translation. These dynamic properties of IF provide mechanisms for regulating their reorganization and assembly in response to the functional requirements of cells. The recent findings that IF and their precursors are frequently associated with signaling molecules have revealed new functions for IF beyond their more traditional roles as mechanical integrators of cells and tissues. 相似文献
150.
PHILIP S WANG MATTHIAS ANGERMEYER GUILHERME BORGES RONNY BRUFFAERTS WAI TAT CHIU GIOVANNI DE GIROLAMO JOHN FAYYAD OYE GUREJE JOSEP MARIA HARO YUEQIN HUANG RONALD C KESSLER VIVIANE KOVESS DAPHNA LEVINSON YOSHIBUMI NAKANE MARK A OAKLEY BROWN JOHAN H ORMEL JOSé POSADA-VILLA SERGIO AGUILAR-GAXIOLA JORDI ALONSO SING LEE STEVEN HEERINGA BETH-ELLEN PENNELL SOMNATH CHATTERJI T. BEDIRHAN üSTüN 《World psychiatry》2007,6(3):177-185
Data are presented on patterns of failure and delay in making initial treatment
contact after first onset of a mental disorder in 15 countries in the World
Health Organization (WHO)''s World Mental Health (WMH) Surveys. Representative
face-to-face household surveys were conducted among 76,012 respondents aged
18 and older in Belgium, Colombia, France, Germany, Israel, Italy, Japan,
Lebanon, Mexico, the Netherlands, New Zealand, Nigeria, People''s Republic
of China (Beijing and Shanghai), Spain, and the United States. The WHO Composite
International Diagnostic Interview (CIDI) was used to assess lifetime DSM-IV
anxiety, mood, and substance use disorders. Ages of onset for individual disorders
and ages of first treatment contact for each disorder were used to calculate
the extent of failure and delay in initial help seeking. The proportion of
lifetime cases making treatment contact in the year of disorder onset ranged
from 0.8 to 36.4% for anxiety disorders, from 6.0 to 52.1% for mood disorders,
and from 0.9 to 18.6% for substance use disorders. By 50 years, the proportion
of lifetime cases making treatment contact ranged from 15.2 to 95.0% for anxiety
disorders, from 7.9 to 98.6% for mood disorders, and from 19.8 to 86.1% for
substance use disorders. Median delays among cases eventually making contact
ranged from 3.0 to 30.0 years for anxiety disorders, from 1.0 to 14.0 years
for mood disorders, and from 6.0 to 18.0 years for substance use disorders.
Failure and delays in treatment seeking were generally greater in developing
countries, older cohorts, men, and cases with earlier ages of onset. These
results show that failure and delays in initial help seeking are pervasive
problems worldwide. Interventions to ensure prompt initial treatment contacts
are needed to reduce the global burdens and hazards of untreated mental disorders. 相似文献