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1.
Clémence L. Gamblin émilie J.-L. Hardy Fran?ois J.-M. Chartier Nicolas Bisson Patrick Laprise 《The Journal of cell biology》2014,204(4):487-495
During epithelial cell polarization, Yurt (Yrt) is initially confined to the lateral membrane and supports the stability of this membrane domain by repressing the Crumbs-containing apical machinery. At late stages of embryogenesis, the apical recruitment of Yrt restricts the size of the apical membrane. However, the molecular basis sustaining the spatiotemporal dynamics of Yrt remains undefined. In this paper, we report that atypical protein kinase C (aPKC) phosphorylates Yrt to prevent its premature apical localization. A nonphosphorylatable version of Yrt dominantly dismantles the apical domain, showing that its aPKC-mediated exclusion is crucial for epithelial cell polarity. In return, Yrt counteracts aPKC functions to prevent apicalization of the plasma membrane. The ability of Yrt to bind and restrain aPKC signaling is central for its role in polarity, as removal of the aPKC binding site neutralizes Yrt activity. Thus, Yrt and aPKC are involved in a reciprocal antagonistic regulatory loop that contributes to segregation of distinct and mutually exclusive membrane domains in epithelial cells. 相似文献
2.
Transpiration and photosynthesis of current-year stems and adult leaves of different deciduous tree species were investigated
to estimate their probable influence on carbon balance. Peridermal transpiration of young stems was found to be rather small
as compared to the transpiration of leaves (stem/leaf like 1/5–1/20). A characteristic that was mainly attributable to the
lower peridermal conductance to water and CO2, which made up only 8–28% of stomatal conductance. Water vapour conductance was significantly lower in stems, but also non-responsive
to PAR, which led to a comparatively higher water use efficiency (WUE, ratio assimilation/transpiration). Thus, although corticular
photosynthesis reached only 11–37% of leaf photosynthesis, it may be a means of improving the carbon balance of stems under
limited water availability. The influence of drought stress on primary photosynthetic reactions was also studied. Under simulated
drought conditions the drying time needed to provoke a 50% reduction (t
50) in dark- and light-adapted PSII efficiency (Fv/Fm, ΔF/Fm′) was up to ten times higher in stems than in leaves. Nevertheless,
up to a relative water deficit (RWD) of around 40–50% dark-adapted PSII efficiency of leaves and stems was rather insensitive
to dehydration, showing that the efficiency of open PS II reaction centres is not impaired. Thus, it may be concluded that
in stems as well as in leaves the primary site of drought damage is at the level of dark enzyme reactions and not within PSII.
However, enduring severe drought caused photoinhibitory damage to the photosynthetic apparatus of leaves and stems; thereby
RWD50 values (= RWD needed to provoke a 50% reduction in Fv/Fm ad ΔF/Fm′) were comparably lower in stems as compared to leaves,
indicating a possibly higher drought sensitivity of the cortex chlorenchyma. 相似文献
3.
Sandrine Cure Florence Bianic Caroline Espinas Helene Hardy Lisa Rosenblatt Timothy Juday 《PloS one》2015,10(5)
Some HIV antiretroviral therapies (ART) have been associated with renal toxicities, which become of increasing concern as HIV-infected patients age and develop comorbidities. The objective of this study was to evaluate the relative impact of atazanavir (ATV)-based regimens on the renal function of adult patients with HIV. We conducted a systematic literature review by searching PubMed, EMBASE, Cochrane library, and the CRD from 2000 until March 2013. Major HIV-related conferences occurring in the past two years were also searched. All randomized clinical trials and large cohort studies assessing renal function in treatment-naïve and/or treatment-experienced HIV patients on ATV-based regimens were included. Fixed-effect mixed-treatment network analyses were carried out on the most frequently reported renal outcomes. 23 studies met the inclusion criteria, and change in estimated glomerular filtration rate (eGFR) from baseline to 48 weeks was identified as the main outcome. Two networks including, respectively, six studies (using the Cockcroft-Gault method) and four studies (using MDRD and CKD-EPI) were analysed. With CG network, ATV/r + TDF/FTC was associated with lower impact on the decline of eGFR than ATV/cobicistat + TDF/FTC but with higher decrease in eGFR than ATV/r + ABC/3TC (difference in mean change from baseline in eGFR repectively +3.67 and –3.89). The use of ATV/cobicistat + TDF/FTC led to a similar decline in eGFR as EVG/cobicistat/TDF/FTC. With respect to third agents combined with TDF/FTC, ATV/r had a lower increase in eGFR in comparison to EFV, and no difference was shown when compared to SQV/r and DRV/r. The effect of ATV-based regimens on renal function at 48 weeks appears similar to other ART regimens and appears to be modest regardless of boosting agent or backbone, although TDF containing backbones consistently leads to greater decline in eGFR. 相似文献
4.
5.
U A Leuenberger J C Hardy M D Herr K S Gray L I Sinoway 《Journal of applied physiology》2001,90(4):1516-1522
Obstructive apnea and voluntary breath holding are associated with transient increases in muscle sympathetic nerve activity (MSNA) and arterial pressure. The contribution of changes in blood flow relative to the contribution of changes in vascular resistance to the apnea-induced transient rise in arterial pressure is unclear. We measured heart rate, mean arterial blood pressure (MAP), MSNA (peroneal microneurography), and femoral artery blood velocity (V(FA), Doppler) in humans during voluntary end-expiratory apnea while they were exposed to room air, hypoxia (10.5% inspiratory fraction of O2), and hyperoxia (100% inspiratory fraction of O2). Changes from baseline of leg blood flow (Q) and vascular resistance (R) were estimated from the following relationships: Q proportional to V(FA), corrected for the heart rate, and R proportional to MAP/Q. During apnea, MSNA rose; this rise in MSNA was followed by a rise in MAP, which peaked a few seconds after resumption of breathing. Responses of MSNA and MAP to apnea were greatest during hypoxia and smallest during hyperoxia (P < 0.05 for both compared with room air breathing). Similarly, apnea was associated with a decrease in Q and an increase in R. The decrease in Q was greatest during hypoxia and smallest during hyperoxia (-25 +/- 3 vs. -6 +/- 4%, P < 0.05), and the increase in R was the greatest during hypoxia and the least during hyperoxia (60 +/- 8 vs. 21 +/- 6%, P < 0.05). Thus voluntary apnea is associated with vasoconstriction, which is in part mediated by the sympathetic nervous system. Because apnea-induced vasoconstriction is most intense during hypoxia and attenuated during hyperoxia, it appears to depend at least in part on stimulation of arterial chemoreceptors. 相似文献
6.
L S Reidl D F Friedman J Goldman R R Hardy L C Jefferies L E Silberstein 《Journal of immunology (Baltimore, Md. : 1950)》1991,147(10):3623-3631
Our laboratory has previously investigated the relationship of autoimmune disease and B cell neoplasia in a patient with a diffuse, well differentiated splenic B cell lymphoma and associated autoimmune hemolysis due to an anti-Pr2 antibody. EBV-immortalized B cell clones, established from this lymphoma, were shown to secrete the same pathologic anti-Pr2 antibody. The antiidiotypic mAb, RI.1, defined a private Id (IdRI.1) of the anti-Pr2 antibody that was related to the Ag-binding site and was expressed by both the lymphoma and derived cell lines. This unique Id was expressed by the majority of splenic tumor B cells and also was conserved over a period of 4 yr. In this report, the structural basis of IdRI.1 expression was investigated by analysis of Id- variants isolated by flow microfluorimetry using RI.1. Six Id- cell lines that secrete IgM kappa but lack Pr2 specificity were generated from an Id+ cell line, LS2. These lines were shown to be related to LS2 and the lymphoma by karyotype and by restriction fragment analysis of Ig gene rearrangements. Shared and unshared nucleotide substitutions in the VH and VL regions of the six independent clones were used to construct a genealogic tree relating the Id- clonal members to a common Id+ precursor. The tree illustrates that the base changes occurred sequentially, suggesting that they were introduced by somatic point mutation. Only one VH CDR3 bp difference from the LS2 nucleic acid sequence is common to all Id- sequences, resulting in an amino acid substitution of cysteine 108 to tyrosine. Taken together, these findings suggest that both the expression of IdRI.1 and Ag binding are affected by a single mutation localized to the D region of the anti-Pr2 antibody. 相似文献
7.
8.
9.
Rowan S Hardy Andrew Filer Mark S Cooper Greg Parsonage Karim Raza Debbie L Hardie Elizabeth H Rabbitt Paul M Stewart Christopher D Buckley Martin Hewison 《Arthritis research & therapy》2006,8(4):R108-10
Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation.
We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of
the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed
in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid
arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were
higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative
to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis
factor-α or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold;
synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-γ was without effect, and there was no difference in 11β-HSD1
expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the
presence of 100 nmol/l cortisone, IL-6 production – a characteristic feature of synovial derived fibroblasts – was significantly
reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor,
emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences
in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations
may play a key role in the predeliction of certain tissues to develop persistent inflammation. 相似文献
10.
Vincent Anquetil Caroline Le Sommer Agn��s M��reau Sandra Hamon Hubert Lerivray Serge Hardy 《The Journal of biological chemistry》2009,284(47):32370-32383
Alternative splicing of 3′-terminal exons plays a critical role in gene expression by producing mRNA with distinct 3′-untranslated regions that regulate their fate and their expression. The Xenopus α-tropomyosin pre-mRNA possesses a composite internal/3′-terminal exon (exon 9A9′) that is differentially processed depending on the embryonic tissue. Exon 9A9′ is repressed in non-muscle tissue by the polypyrimidine tract binding protein, whereas it is selected as a 3′-terminal or internal exon in myotomal cells and adult striated muscles, respectively. We report here the identification of an intronic regulatory element, designated the upstream terminal exon enhancer (UTE), that is required for the specific usage of exon 9A9′ as a 3′-terminal exon in the myotome. We demonstrate that polypyrimidine tract binding protein prevents the activity of UTE in non-muscle cells, whereas a subclass of serine/arginine rich (SR) proteins promotes the selection of exon 9A9′ in a UTE-dependent way. Morpholino-targeted blocking of UTE in the embryo strongly reduced the inclusion of exon 9A9′ as a 3′-terminal exon in the endogenous mRNA, demonstrating the function of UTE under physiological circumstances. This strategy allowed us to reveal a splicing pathway that generates a mRNA with no in frame stop codon and whose steady-state level is translation-dependent. This result suggests that a non-stop decay mechanism participates in the strict control of the 3′-end processing of the α-tropomyosin pre-mRNA. 相似文献