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141.
John C. Craig George Geof H. Givens Lara Horstmann Robert Suydam Kayla Scheimreif Raphaela Stimmelmayr Gay Sheffield Todd L. Sformo Brian Person Andrew Von Duyke Leandra Sousa Rita M. Frantz Raymond Tarpley 《Marine Mammal Science》2024,40(2):e13079
Data from Bering-Chukchi-Beaufort Seas bowhead whales (Balaena mysticetus), harvested during 1973–2021 by aboriginal subsistence hunters, were used to estimate reproductive parameters: length at sexual maturity (LSM), age at sexual maturity (ASM), pregnancy rate (PR), and calving interval. Sexual maturity (N = 187 females) was determined from the presence/absence of corpora in the ovaries, or a fetus. Using sampling bias-corrected logistic regression, LSM was estimated at 13.5 m, 95% CI [13.0, 13.8]. There was a downward trend in LSM over time, statistically significant with one method but marginal with another. A growth model translated this estimate to an ASM estimate of 23.5 years, 95% CI [20.4, 26.7]. Pregnancy rate was determined from mature females (N = 125), and from a subset limited to certain autumn-caught whales (n = 37) to reduce bias. The PR was estimated at 0.46 globally, 95% CI [0.36, 0.55] and 0.38 for the autumn sample, 95% CI [0.20, 0.51]. Both estimated PRs are consistent with a 3-year calving interval, because the larger estimate includes two cohorts of pregnant whales harvested in spring, and bowhead whale gestation is longer than 12 months. These analyses represent the most conclusive empirical estimates of ASM, LSM, and PR for this bowhead whale stock from the largest available data sets to date. 相似文献
142.
Osteoclasts, isolated from the endosteum of 2.5- to 3-week-old chickens, were treated with acridine orange, a hydrogen ion concentration-sensitive fluorescent dye, in order to monitor changes in acid production. The adenylate cyclase inhibitor, alloxan, blocked parathyroid hormone (PTH)-stimulated acid production. Dibutyryl cyclic adenosine monophosphate, a membrane-permeant form of cyclic adenosine monophosphate, mimicked the PTH effect. Bisindolylmaleimide, a specific inhibitor of protein kinase C (PKC), blocked the initial stimulation (15, 30, and 60 min) of acid production by PTH but had no effect on long-term stimulation (120 min). Confocal microscopy of osteoclasts stained with fluorescein-conjugated bisindolylmaleimide revealed a shift in location of PKC from the cytoplasm to the plasma membrane region after treatment with parathyroid hormone. The results of these studies support the hypothesis that PTH regulation of acid production in osteoclasts involves both adenylate cyclase and PKC as effectors. J. Cell. Biochem. 65:565–573. © 1997 Wiley-Liss Inc. 相似文献
143.
François-René Alexandre Eric Badaroux John P. Bilello Stéphanie Bot Tony Bouisset Guillaume Brandt Sylvie Cappelle Christopher Chapron Dominique Chaves Thierry Convard Clément Counor Daniel Da Costa David Dukhan Marion Gay Gilles Gosselin Jean-François Griffon Kusum Gupta Brenda Hernandez-Santiago Cyril B. Dousson 《Bioorganic & medicinal chemistry letters》2017,27(18):4323-4330
Herein we describe the discovery of IDX21437 35b, a novel RP d-aminoacid-based phosphoramidate prodrug of 2′-α-chloro-2′-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells. Furthermore, due to its metabolic activation, 35b was efficiently processed in liver cells compared to other cell types, including human cardiomyocytes. The selected RP diastereoisomeric configuration of 35b was assigned by X-ray structural determination. 35b is currently in Phase II clinical trials for the treatment of HCV infection. 相似文献
144.
Tropical soils degraded by slash‐and‐burn cultivation can be recultivated when amended with ashes and compost 下载免费PDF全文
Justine Marie Gay‐des‐Combes Clara Sanz Carrillo Bjorn Jozef Maria Robroek Vincent Eric Jules Jassey Robert Thomas Edmund Mills Muhammad Saleem Arif Leia Falquet Emmanuel Frossard Alexandre Buttler 《Ecology and evolution》2017,7(14):5378-5388
In many tropical regions, slash‐and‐burn agriculture is considered as a driver of deforestation; the forest is converted into agricultural land by cutting and burning the trees. However, the fields are abandoned after few years because of yield decrease and weed invasion. Consequently, new surfaces are regularly cleared from the primary forest. We propose a reclamation strategy for abandoned fields allowing and sustaining re‐cultivation. In the dry region of south‐western Madagascar, we tested, according to a split‐plot design, an alternative selective slash‐and‐burn cultivation technique coupled with compost amendment on 30–year‐old abandoned fields. Corn plants (Zea mays L.) were grown on four different types of soil amendments: no amendment (control), compost, ashes (as in traditional slash‐and‐burn cultivation), and compost + ashes additions. Furthermore, two tree cover treatments were applied: 0% tree cover (as in traditional slash‐and‐burn cultivation) and 50% tree cover (selective slash‐and‐burn). Both corn growth and soil fertility parameters were monitored during the growing season 2015 up to final harvest. The amendment compost + ashes strongly increased corn yield, which was multiplied by 4–5 in comparison with ashes or compost alone, reaching 1.5 t/ha compared to 0.25 and 0.35 t/ha for ashes and compost, respectively. On control plots, yield was negligible as expected on these degraded soils. Structural equation modeling evidenced that compost and ashes were complementary fertilizing pathways promoting soil fertility through positive effects on soil moisture, pH, organic matter, and microbial activity. Concerning the tree cover treatment, yield was reduced on shaded plots (50% tree cover) compared to sunny plots (0% tree cover) for all soil amendments, except ashes. To conclude, our results provide empirical evidence on the potential of recultivating tropical degraded soils with compost and ashes. This would help mitigating deforestation of the primary forest by increasing lifespan of agricultural lands. 相似文献
145.
Sister kinetochore recapture in fission yeast occurs by two distinct mechanisms, both requiring Dam1 and Klp2 总被引:3,自引:1,他引:2 下载免费PDF全文
Gachet Y Reyes C Courthéoux T Goldstone S Gay G Serrurier C Tournier S 《Molecular biology of the cell》2008,19(4):1646-1662
In eukaryotic cells, proper formation of the spindle is necessary for successful cell division. We have studied chromosome recapture in the fission yeast Schizosaccharomyces pombe. We show by live cell analysis that lost kinetochores interact laterally with intranuclear microtubules (INMs) and that both microtubule depolymerization (end-on pulling) and minus-end-directed movement (microtubule sliding) contribute to chromosome retrieval to the spindle pole body (SPB). We find that the minus-end-directed motor Klp2 colocalizes with the kinetochore during its transport to the SPB and contributes to the effectiveness of retrieval by affecting both end-on pulling and lateral sliding. Furthermore, we provide in vivo evidence that Dam1, a component of the DASH complex, also colocalizes with the kinetochore during its transport and is essential for its retrieval by either of these mechanisms. Finally, we find that the position of the unattached kinetochore correlates with the size and orientation of the INMs, suggesting that chromosome recapture may not be a random process. 相似文献
146.
The calcium phosphate-based skeleton of vertebrates serves as the major reservoir for metabolically available calcium ions. The skeleton is formed by osteoblasts which first secrete a proteinaceous matrix and then provide Ca++ for the calcification process. The two calcium efflux ports found in most cells are the plasma membrane Ca-ATPase (PMCA) and the sodium-calcium exchanger (NCX). In osteoblasts, PMCA and NCX are located on opposing sides of the cell with NCX facing the mineralizing bone surface. Two isoforms of NCX have been identified in osteoblasts NCX1, and NCX3. The purpose of this study was to determine the extent to which each of the two NCX isoforms support delivery of Ca++ into sites of calcification and to discern if one could compensate for the other. SiRNA technology was used to knockdown each isoform separately in MC3T3-E1 osteoblasts. Osteoblasts in which either NCX1 or NCX3 was impaired were tested for Ca++ efflux using the Ca++ specific fluorophore, fluo-4, in a sodium-dependent calcium uptake assay adapted for image analysis. NCX3 was found to serve as a major contributor of Ca++ translocation out of osteoblasts into calcifying bone matrix. NCX1 had little to no involvement. 相似文献
147.
Dale E. Tronrud Jianzhong Wen Leslie Gay Robert E. Blankenship 《Photosynthesis research》2009,100(2):79-87
The absorbance spectrum of the Fenna-Matthews-Olson protein—a component of the antenna system of Green Sulfur Bacteria—is always one of two types, depending on the species of the source organism. The FMO from Prosthecochloris aestuarii 2K has a spectrum of type 1 while that from Chlorobaculum tepidum is of type 2. The previously reported crystal structures for these two proteins did not disclose any rationale that would explain their spectral differences. We have collected a 1.3 Å X-ray diffraction dataset of the FMO from Prosthecochloris aestuarii 2K, which has allowed us to identify an additional Bacteriochlorophyll-a molecule with chemical attachments to both sides of the central magnesium atom. A new analysis of the previously published X-ray data for the Chlorobaculum tepidum FMO shows the presence of a Bacteriochlorophyll-a molecule in an equivalent location but with a chemical attachment from only one side. This difference in binding is shown to be predictive of the spectral type of the FMO. 相似文献
148.
149.
150.
E-Chiang Lee Urvi Desai Gennady Gololobov Seokjoo Hong Xiao Feng Xuan-Chuan Yu Jason Gay Nat Wilganowski Cuihua Gao Ling-Ling Du Joan Chen Yi Hu Sharon Zhao Laura Kirkpatrick Matthias Schneider Brian P. Zambrowicz Greg Landes David R. Powell William K. Sonnenburg 《The Journal of biological chemistry》2009,284(20):13735-13745
Angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) are
secreted proteins that regulate triglyceride (TG) metabolism in part by
inhibiting lipoprotein lipase (LPL). Recently, we showed that treatment of
wild-type mice with monoclonal antibody (mAb) 14D12, specific for ANGPTL4,
recapitulated the Angptl4 knock-out (-/-) mouse phenotype of reduced
serum TG levels. In the present study, we mapped the region of mouse ANGPTL4
recognized by mAb 14D12 to amino acids
Gln29–His53, which we designate as specific
epitope 1 (SE1). The 14D12 mAb prevented binding of ANGPTL4 with LPL,
consistent with its ability to neutralize the LPL-inhibitory activity of
ANGPTL4. Alignment of all angiopoietin family members revealed that a sequence
similar to ANGPTL4 SE1 was present only in ANGPTL3, corresponding to amino
acids Glu32–His55. We produced a mouse mAb against
this SE1-like region in ANGPTL3. This mAb, designated 5.50.3, inhibited the
binding of ANGPTL3 to LPL and neutralized ANGPTL3-mediated inhibition of LPL
activity in vitro. Treatment of wild-type as well as hyperlipidemic
mice with mAb 5.50.3 resulted in reduced serum TG levels, recapitulating the
lipid phenotype found in Angptl3-/- mice. These results
show that the SE1 region of ANGPTL3 and ANGPTL4 functions as a domain
important for binding LPL and inhibiting its activity in vitro and
in vivo. Moreover, these results demonstrate that therapeutic
antibodies that neutralize ANGPTL4 and ANGPTL3 may be useful for treatment of
some forms of hyperlipidemia.Lipoprotein lipase
(LPL)5 plays a pivotal
role in lipid metabolism by catalyzing the hydrolysis of plasma triglycerides
(TGs). LPL is likely to be regulated by mechanisms that depend on nutritional
status and on the tissue in which it is expressed
(1–3).
Two secreted proteins, angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4
(ANGPTL4), play important roles in the regulation of LPL activity
(4,
5). ANGPTL3 and ANGPTL4 consist
of a signal peptide, an N-terminal segment containing coiled-coil domains, and
a C-terminal fibrinogen-like domain. The N-terminal segment as well as
full-length ANGPTL3 and ANGPTL4 have been shown to inhibit LPL activity, and
deletion of the N-terminal segment of ANGPTL3 and ANGPTL4 resulted in total
loss of LPL-inhibiting activity
(6,
7). These observations clearly
indicate that the N-terminal region of ANGPTL4 contains the functional domain
that inhibits LPL and affects plasma lipid levels. The coiled-coil domains
have been proposed to be responsible for oligomerization
(8); however, it is not known
whether the coiled-coil domains directly mediate the inhibition of LPL
activity.To define the physiological role of ANGPTL4 more clearly, we characterized
the pharmacological consequences of ANGPTL4 inhibition in mice treated with
the ANGPTL4-neutralizing monoclonal antibody (mAb) 14D12
(9). Injection of mAb 14D12
significantly lowered fasting TG levels in C57BL/6J mice relative to levels in
C57BL/6J mice treated with an isotype-matched anti-KLH control (KLH) mAb
(9). These reduced TG values
were similar to decreases in fasting plasma TG levels measured in
Angptl4 knock-out (-/-) mice. This study demonstrated that mAb 14D12
is a potent ANGPTL4-neutralizing antibody that is able to inhibit systemic
ANGPTL4 activity and thereby recapitulate the reduced lipid phenotype found in
Angptl4-/- mice. The readily apparent pharmacological
effect of mAb 14D12 prompted new questions about the epitope recognized by mAb
14D12 and how this antibody-antigen binding event affected ANGPTL4 function as
an LPL inhibitor.Although ANGPTL4 is able to interact directly with LPL
(10), it is not clear which
amino acids within ANGPTL4 mediate this interaction. Here we show that amino
acids Gln29–His53 of mANGPTL4 contain the epitope
for mAb 14D12. This region, hereby designated specific epitope 1 (SE1), also
defines a domain that mediates the interaction between ANGPTL4 and LPL and the
subsequent inactivation of LPL. With this information we present evidence that
ANGPTL3 also contains an SE1 region, and with antibodies specifically reactive
with ANGPTL3 SE1 we examine whether the ANGPTL3 SE1 region is involved in LPL
binding and inhibition. We also determined whether treatment of C57BL/6 mice
with an anti-ANGPTL3 SE1 mAb can recapitulate the phenotype of lower serum TG
and cholesterol levels found in Angptl3-/- mice. Finally
we tested the therapeutic potential of an anti-ANGPTL3 SE1 mAb for treatment
of hyperlipidemia in apolipoprotein E-/-
(ApoE-/-) or low density lipoprotein
receptor-/- (LDLr-/-) mice. 相似文献