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91.
Kathleen D'Halluin Chantal Vanderstraeten Jolien Van Hulle Joanna Rosolowska Ilse Van Den Brande Anouk Pennewaert Kristel D'Hont Martine Bossut Derek Jantz Rene Ruiter Jean Broadhvest 《Plant biotechnology journal》2013,11(8):933-941
Recent developments of tools for targeted genome modification have led to new concepts in how multiple traits can be combined. Targeted genome modification is based on the use of nucleases with tailor‐made specificities to introduce a DNA double‐strand break (DSB) at specific target loci. A re‐engineered meganuclease was designed for specific cleavage of an endogenous target sequence adjacent to a transgenic insect control locus in cotton. The combination of targeted DNA cleavage and homologous recombination–mediated repair made precise targeted insertion of additional trait genes (hppd, epsps) feasible in cotton. Targeted insertion events were recovered at a frequency of about 2% of the independently transformed embryogenic callus lines. We further demonstrated that all trait genes were inherited as a single genetic unit, which will simplify future multiple‐trait introgression. 相似文献
92.
Background
While evaluation of liver function in preclinical animal studies is commonly performed at selected time-points by invasive determination of the liver/body weight ratio and histological analyses, the validation of longitudinal measurement tools for monitoring liver function are of major interest.Aims
To longitudinally evaluate serum cholinesterase (CHE) and total serum bilirubin (TSB) levels as non-invasive markers to determine injury- and partial hepatectomy (PHx)-induced alterations of liver function in rats.Methods
Male and female Lewis rats were subjected to either methionine/choline deficient (MCD) diet or treatment with FOLFOX chemotherapy prior to PHx. Body weight and CHE/TSB levels are determined weekly. Following PHx and at the study end, histological analyses of liver tissue are performed.Results
Following MCD diet, but not after FOLFOX chemotherapy treatment, results indicate gender-specific alterations in serum CHE levels and gender-independent alterations in TSB levels. Likewise, histological analyses of resected liver parts indicate significant liver injury following MCD-diet, but not following FOLFOX treatment. While TSB levels rapidly recover following MCD diet/FOLFOX treatment combined with a PHx, serum CHE levels are subject to significant model- and gender-specific differences, despite full histopathological recovery of liver tissue.Conclusions
Longitudinal measurements of serum CHE levels and TSB levels in rats are highly complementary as non-invasive parameters for evaluation of liver injury and/or recovery. 相似文献93.
Samuel J. Clark Kathleen Kahn Brian Houle Adriane Arteche Mark A. Collinson Stephen M. Tollman Alan Stein 《PLoS medicine》2013,10(3)
Background
There is evidence that a young child''s risk of dying increases following the mother''s death, but little is known about the risk when the mother becomes very ill prior to her death. We hypothesized that children would be more likely to die during the period several months before their mother''s death, as well as for several months after her death. Therefore we investigated the relationship between young children''s likelihood of dying and the timing of their mother''s death and, in particular, the existence of a critical period of increased risk.Methods and Findings
Data from a health and socio-demographic surveillance system in rural South Africa were collected on children 0–5 y of age from 1 January 1994 to 31 December 2008. Discrete time survival analysis was used to estimate children''s probability of dying before and after their mother''s death, accounting for moderators. 1,244 children (3% of sample) died from 1994 to 2008. The probability of child death began to rise 6–11 mo prior to the mother''s death and increased markedly during the 2 mo immediately before the month of her death (odds ratio [OR] 7.1 [95% CI 3.9–12.7]), in the month of her death (OR 12.6 [6.2–25.3]), and during the 2 mo following her death (OR 7.0 [3.2–15.6]). This increase in the probability of dying was more pronounced for children whose mothers died of AIDS or tuberculosis compared to other causes of death, but the pattern remained for causes unrelated to AIDS/tuberculosis. Infants aged 0–6 mo at the time of their mother''s death were nine times more likely to die than children aged 2–5 y. The limitations of the study included the lack of knowledge about precisely when a very ill mother will die, a lack of information about child nutrition and care, and the diagnosis of AIDS deaths by verbal autopsy rather than serostatus.Conclusions
Young children in lower income settings are more likely to die not only after their mother''s death but also in the months before, when she is seriously ill. Interventions are urgently needed to support families both when the mother becomes very ill and after her death. Please see later in the article for the Editors'' Summary 相似文献94.
95.
Géraldine De Muylder Sylvie Daulouède Laurence Lecordier Pierrick Uzureau Yannick Morias Jan Van Den Abbeele Guy Caljon Michel Hérin Philippe Holzmuller Silla Semballa Pierrette Courtois Luc Vanhamme Beno?t Stijlemans Patrick De Baetselier Michael P. Barrett Jillian L. Barlow Andrew N. J. McKenzie Luke Barron Thomas A. Wynn Alain Beschin Philippe Vincendeau Etienne Pays 《PLoS pathogens》2013,9(10)
Background
In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.Methodology/Principal findings
By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO) synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.Conclusion
A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity. 相似文献96.
Cara N. Halldin Eva Suarthana Kathleen B. Fedan Yi-Chun Lo George Turabelidze Kathleen Kreiss 《PloS one》2013,8(2)
Background
Bronchiolitis obliterans, an irreversible lung disease, was first associated with inhalation of butter flavorings (diacetyl) in workers at a microwave popcorn company. Excess rates of lung-function abnormalities were related to cumulative diacetyl exposure. Because information on potential excess mortality would support development of permissible exposure limits for diacetyl, we investigated respiratory-associated mortality during 2000–2011 among current and former workers at this company who had exposure to flavorings and participated in cross-sectional surveys conducted between 2000–2003.Methods
We ascertained workers'' vital status through a Social Security Administration search. Causes of death were abstracted from death certificates. Because bronchiolitis obliterans is not coded in the International Classification of Disease 10th revision (ICD-10), we identified respiratory mortality decedents with ICD-10 codes J40–J44 which encompass bronchitis (J40), simple and mucopurulent chronic bronchitis (J41), unspecified chronic bronchitis (J42), emphysema (J43), and other chronic obstructive pulmonary disease (COPD) (J44). We calculated expected number of deaths and standardized mortality ratios (SMRs) with 95% confidence intervals (CI) to determine if workers exposed to diacetyl experienced greater respiratory mortality than expected.Results
We identified 15 deaths among 511 workers. Based on U.S. population estimates, 17.39 deaths were expected among these workers (SMR = 0.86; CI:0.48-1.42). Causes of death were available for 14 decedents. Four deaths among production and flavor mixing workers were documented to have a multiple cause of ‘other COPD’ (J44), while 0.98 ‘other COPD’-associated deaths were expected (SMR = 4.10; CI:1.12–10.49). Three of the 4 ‘other COPD’-associated deaths occurred among former workers and workers employed before the company implemented interventions reducing diacetyl exposure in 2001.Conclusion
Workers at the microwave popcorn company experienced normal rates of all-cause mortality but higher rates of COPD-associated mortality, especially workers employed before the company reduced diacetyl exposure. The demonstrated excess in COPD-associated mortality suggests continued efforts to lower flavoring exposure are prudent. 相似文献97.
Il-Young Hwang Chung Park Thuyvi Luong Kathleen A. Harrison Lutz Birnbaumer John H. Kehrl 《PloS one》2013,8(8)
B lymphocytes are compartmentalized within lymphoid organs. The organization of these compartments depends upon signaling initiated by G-protein linked chemoattractant receptors. To address the importance of the G-proteins Gαi2 and Gαi3 in chemoattractant signaling we created mice lacking both proteins in their B lymphocytes. While bone marrow B cell development and egress is grossly intact; mucosal sites, splenic marginal zones, and lymph nodes essentially lack B cells. There is a partial block in splenic follicular B cell development and a 50-60% reduction in splenic B cells, yet normal numbers of splenic T cells. The absence of Gαi2 and Gαi3 in B cells profoundly disturbs the architecture of lymphoid organs with loss of B cell compartments in the spleen, thymus, lymph nodes, and gastrointestinal tract. This results in a severe disruption of B cell function and a hyper-IgM like syndrome. Beyond the pro-B cell stage, B cells are refractory to chemokine stimulation, and splenic B cells are poorly responsive to antigen receptor engagement. Gαi2 and Gαi3 are therefore critical for B cell chemoattractant receptor signaling and for normal B cell function. These mice provide a worst case scenario of the consequences of losing chemoattractant receptor signaling in B cells. 相似文献
98.
Mariano Alvarez Andrew Bleich Kathleen Donohue 《Evolution; international journal of organic evolution》2020,74(10):2265-2280
Phenotypes respond to environments experienced directly by an individual, via phenotypic plasticity, or to the environment experienced by ancestors, via transgenerational environmental effects. The adaptive value of environmental effects depends not only on the strength and direction of the induced response but also on how long the response persists within and across generations, and how stably it is expressed across environments that are encountered subsequently. Little is known about the genetic basis of those distinct components, or even whether they exhibit genetic variation. We tested for genetic differences in the inducibility, temporal persistence, and environmental stability of transgenerational environmental effects in Arabidopsis thaliana. Genetic variation existed in the inducibility of transgenerational effects on traits expressed across the life cycle. Surprisingly, the persistence of transgenerational effects into the third generation was uncorrelated with their induction in the second generation. Although environmental effects for some traits in some genotypes weakened over successive generations, others were stronger or even in the opposite direction in more distant generations. Therefore, transgenerational effects in more distant generations are not merely caused by the retention or dissipation of those expressed in prior generations, but they may be genetically independent traits with the potential to evolve independently. 相似文献
99.
The actinobacterial transcription factor RbpA binds to the principal sigma subunit of RNA polymerase
100.