全文获取类型
收费全文 | 4410篇 |
免费 | 370篇 |
国内免费 | 2篇 |
专业分类
4782篇 |
出版年
2024年 | 5篇 |
2023年 | 29篇 |
2022年 | 75篇 |
2021年 | 152篇 |
2020年 | 71篇 |
2019年 | 76篇 |
2018年 | 114篇 |
2017年 | 93篇 |
2016年 | 152篇 |
2015年 | 240篇 |
2014年 | 280篇 |
2013年 | 325篇 |
2012年 | 408篇 |
2011年 | 362篇 |
2010年 | 250篇 |
2009年 | 204篇 |
2008年 | 272篇 |
2007年 | 249篇 |
2006年 | 220篇 |
2005年 | 177篇 |
2004年 | 196篇 |
2003年 | 188篇 |
2002年 | 161篇 |
2001年 | 28篇 |
2000年 | 25篇 |
1999年 | 43篇 |
1998年 | 38篇 |
1997年 | 29篇 |
1996年 | 22篇 |
1995年 | 21篇 |
1994年 | 23篇 |
1993年 | 26篇 |
1992年 | 17篇 |
1991年 | 18篇 |
1990年 | 19篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 10篇 |
1986年 | 15篇 |
1985年 | 7篇 |
1984年 | 12篇 |
1983年 | 10篇 |
1982年 | 15篇 |
1981年 | 9篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 11篇 |
1977年 | 8篇 |
1974年 | 9篇 |
1965年 | 5篇 |
排序方式: 共有4782条查询结果,搜索用时 0 毫秒
161.
Milly Marston Jessica Nakiyingi-Miiro Victoria Hosegood Tom Lutalo Baltazar Mtenga Basia Zaba 《PloS one》2016,11(3)
Background
UNAIDS official estimates of national HIV prevalence are based on trends observed in antenatal clinic surveillance, after adjustment for the reduced fertility of HIV positive women. Uptake of ART may impact on the fertility of HIV positive women, implying a need to re-estimate the adjustment factors used in these calculations. We analyse the effect of antiretroviral therapy (ART) provision on population-level fertility in Southern and East Africa, comparing trends in HIV infected women against the secular trends observed in uninfected women.Methods
We used fertility data from four community-based demographic and HIV surveillance sites: Kisesa (Tanzania), Masaka and Rakai (Uganda) and uMkhanyakude (South Africa). All births to women aged 15–44 years old were included in the analysis, classified by mother’s age and HIV status at time of birth, and ART availability in the community. Calendar time period of data availability relative to ART Introduction varied across the sites, from 5 years prior to ART roll-out, to 9 years after. Calendar time was classified according to ART availability, grouped into pre ART, ART introduction (available in at least one health facility serving study site) and ART available (available in all designated health facilities serving study site). We used Poisson regression to calculate age adjusted fertility rate ratios over time by HIV status, and investigated the interaction between ART period and HIV status to ascertain whether trends over time were different for HIV positive and negative women.Results
Age-adjusted fertility rates declined significantly over time for HIV negative women in all four studies. However HIV positives either had no change in fertility (Masaka, Rakai) or experienced a significant increase over the same period (Kisesa, uMkhanyakude). HIV positive fertility was significantly lower than negative in both the pre ART period (age adjusted fertility rate ratio (FRR) range 0.51 95%CI 0.42–0.61 to 0.73 95%CI 0.64–0.83) and when ART was widely available (FRR range 0.57 95%CI 0.52–0.62 to 0.83 95%CI 0.78–0.87), but the difference has narrowed. The interaction terms describing the difference in trends between HIV positives and negatives are generally significant.Conclusions
Differences in fertility between HIV positive and HIV negative women are narrowing over time as ART becomes more widely available in these communities. Routine adjustment of ANC data for estimating national HIV prevalence will need to allow for the impact of treatment. 相似文献162.
Andrea Fernanda Gil Lorenzo Victoria Bocanegra María Eugenia Benardon Valeria Cacciamani Patricia G. Vallés 《Cell stress & chaperones》2014,19(1):115-134
A series of signaling cascades are activated after angiotensin II binds to angiotensin II type I receptor (AT1R), a peptide that is an important mediator of oxidative stress. Hsp70 regulates a diverse set of signaling pathways through interactions with proteins. Here, we tested the hypothesis of angiotensin II AT1R inhibition effect on Hsp70 interaction with Nox4/p22phox complex and Hsp70 leading to actin cytoskeleton modulation in spontaneously hypertensive rats (SHR) vascular smooth muscle cells (VSMCs). SHR and Wistar–Kyotto rats (VSMCs from 8 to 10 weeks) were stimulated with angiotensin II (100 nmol/L) for 15 min (AII), treated with losartan (100 nmol/L) for 90 min (L), and with losartan for 90 min plus angiotensin in the last 15 min (L + AII). Whereas SHR VSMCs exposure to angiotensin II overexpressed AT1R and Nox4 nicotinamide–adenine dinucleotide phosphate (NADPH) oxidase and slightly downregulated caveolin-1 expression, losartan decreased AT1R protein levels and increased caveolin-1 and Hsp70 expression in SHR VSMC membranes. Immunoprecipitation and immunofluorescence confocal microscopy proved interaction and colocalization of membrane translocated Hsp70 and Nox4/p22phox. Increased levels of Hsp70 contrast with the decreased immunoprecipitation of Nox4/p22phox and RhoA in membranes from SHR VSMCs (L) vs SHR VSMCs (AII). Hsp72 depletion resulted in higher Nox4 expression and increased NADPH oxidase activity in VSMCs (L + AII) from SHR when contrasted with nontransfected VSMCs (L + AII). After Hsp72 knockdown in SHR VSMCs, losartan could not impair angiotensin II-enhanced stress fiber formation and focal adhesion assembly. In conclusion, our data showing a negative regulation of Hsp70 on Nox4/p22phox demonstrates a possible mechanism in explaining the antioxidative function joined to cytoskeletal integrity modulation within the effects of losartan in VSMCs from SHR. 相似文献
163.
David J. Rosenman Yao‐ming Huang Ke Xia Keith Fraser Victoria E. Jones Colleen M. Lamberson Patrick Van Roey Wilfredo Colón Christopher Bystroff 《Protein science : a publication of the Protein Society》2014,23(4):400-410
Wild‐type green fluorescent protein (GFP) folds on a time scale of minutes. The slow step in folding is a cis–trans peptide bond isomerization. The only conserved cis‐peptide bond in the native GFP structure, at P89, was remodeled by the insertion of two residues, followed by iterative energy minimization and side chain design. The engineered GFP was synthesized and found to fold faster and more efficiently than its template protein, recovering 50% more of its fluorescence upon refolding. The slow phase of folding is faster and smaller in amplitude, and hysteresis in refolding has been eliminated. The elimination of a previously reported kinetically trapped state in refolding suggests that X‐P89 is trans in the trapped state. A 2.55 Å resolution crystal structure revealed that the new variant contains only trans‐peptide bonds, as designed. This is the first instance of a computationally remodeled fluorescent protein that folds faster and more efficiently than wild type. 相似文献
164.
165.
166.
167.
Ines Pires da Silva Isabella C. Glitza Lauren E. Haydu Romany Johnpulle Patricia D. Banks George D. Grass Simone M. A. Goldinger Jessica L. Smith Ashlyn S. Everett Peter Koelblinger Rachel Roberts‐Thomson Michael Millward Victoria G. Atkinson Alexander Guminski Rony Kapoor Robert M. Conry Matteo S. Carlino Wei Wang Mark J. Shackleton Zeynep Eroglu Serigne Lo Angela M. Hong Georgina V. Long Douglas B. Johnson Alexander M. Menzies 《Pigment cell & melanoma research》2019,32(4):553-563
168.
Dimorphic sex chromosomes create problems. Males of many species, including Drosophila, are heterogametic, with dissimilar X and Y chromosomes. The essential process of dosage compensation modulates the expression of X-linked genes in one sex to maintain a constant ratio of X to autosomal expression. This involves the regulation of hundreds of dissimilar genes whose only shared property is chromosomal address. Drosophila males dosage compensate by up regulating X-linked genes 2 fold. This is achieved by the Male Specific Lethal (MSL) complex, which is recruited to genes on the X chromosome and modifies chromatin to increase expression. How the MSL complex is restricted to X-linked genes remains unknown. Recent studies of sex chromosome evolution have identified a central role for 2 types of repetitive elements in X recognition. Helitrons carrying sites that recruit the MSL complex have expanded across the X chromosome in at least one Drosophila species.1 Our laboratory found that siRNA from an X-linked satellite repeat promotes X recognition by a yet unknown mechanism.2 The recurring adoption of repetitive elements as X-identify elements suggests that the large and mysterious fraction of the genome called “junk” DNA is actually instrumental in the evolution of sex chromosomes. 相似文献
169.
170.
Souha Berriri Ana Victoria Garcia Nicolas Frei dit Frey Wilfried Rozhon Stéphanie Pateyron Nathalie Leonhardt Jean-Luc Montillet Jeffrey Leung Heribert Hirt Jean Colcombet 《The Plant cell》2012,24(10):4281-4293
Plant mitogen-activated protein kinases (MAPKs) are involved in important processes, including stress signaling and development. In a functional yeast screen, we identified mutations that render Arabidopsis thaliana
MAPKs constitutively active (CA). Importantly, CA-MAPKs maintain their specificity toward known activators and substrates. As a proof-of-concept, Arabidopsis MAPK4 (MPK4) function in plant immunity was investigated. In agreement with the phenotype of mpk4 mutants, CA-MPK4 plants were compromised in pathogen-induced salicylic acid accumulation and disease resistance. MPK4 activity was found to negatively regulate pathogen-associated molecular pattern-induced reactive oxygen species production but had no impact on callose deposition, indicating that CA-MPK4 allows discriminating between processes regulated by MPK4 activity from processes indirectly affected by mpk4 mutation. Finally, MPK4 activity was also found to compromise effector-triggered immunity conditioned by the Toll Interleukin-1 Receptor–nucleotide binding (NB)–Leu-rich repeat (LRR) receptors RPS4 and RPP4 but not by the coiled coil–NB-LRR receptors RPM1 and RPS2. Overall, these data reveal important insights on how MPK4 regulates plant defenses and establishes that CA-MAPKs offer a powerful tool to analyze the function of plant MAPK pathways. 相似文献