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951.
952.
Monika Witusik Sylwester Piaskowski Krystyna Hulas-Bigoszewska Magdalena Zakrzewska Sylwia M Gresner S Ausim Azizi Barbara Krynska Pawel P Liberski Piotr Rieske 《BMC biotechnology》2008,8(1):56
Background
Although extensive research has been performed to control differentiation of neural stem cells – still, the response of those cells to diverse cell culture conditions often appears to be random and difficult to predict. To this end, we strived to obtain stabilized protocol of NHA cells differentiation – allowing for an increase in percentage yield of neuronal cells. 相似文献953.
Winiarska M Bil J Wilczek E Wilczynski GM Lekka M Engelberts PJ Mackus WJ Gorska E Bojarski L Stoklosa T Nowis D Kurzaj Z Makowski M Glodkowska E Issat T Mrowka P Lasek W Dabrowska-Iwanicka A Basak GW Wasik M Warzocha K Sinski M Gaciong Z Jakobisiak M Parren PW Golab J 《PLoS medicine》2008,5(3):e64
Background
Rituximab is used in the treatment of CD20+ B cell lymphomas and other B cell lymphoproliferative disorders. Its clinical efficacy might be further improved by combinations with other drugs such as statins that inhibit cholesterol synthesis and show promising antilymphoma effects. The objective of this study was to evaluate the influence of statins on rituximab-induced killing of B cell lymphomas.Methods and Findings
Complement-dependent cytotoxicity (CDC) was assessed by MTT and Alamar blue assays as well as trypan blue staining, and antibody-dependent cellular cytotoxicity (ADCC) was assessed by a 51Cr release assay. Statins were found to significantly decrease rituximab-mediated CDC and ADCC of B cell lymphoma cells. Incubation of B cell lymphoma cells with statins decreased CD20 immunostaining in flow cytometry studies but did not affect total cellular levels of CD20 as measured with RT-PCR and Western blotting. Similar effects are exerted by other cholesterol-depleting agents (methyl-β-cyclodextrin and berberine), but not filipin III, indicating that the presence of plasma membrane cholesterol and not lipid rafts is required for rituximab-mediated CDC. Immunofluorescence microscopy using double staining with monoclonal antibodies (mAbs) directed against a conformational epitope and a linear cytoplasmic epitope revealed that CD20 is present in the plasma membrane in comparable amounts in control and statin-treated cells. Atomic force microscopy and limited proteolysis indicated that statins, through cholesterol depletion, induce conformational changes in CD20 that result in impaired binding of anti-CD20 mAb. An in vivo reduction of cholesterol induced by short-term treatment of five patients with hypercholesterolemia with atorvastatin resulted in reduced anti-CD20 binding to freshly isolated B cells.Conclusions
Statins were shown to interfere with both detection of CD20 and antilymphoma activity of rituximab. These studies have significant clinical implications, as impaired binding of mAbs to conformational epitopes of CD20 elicited by statins could delay diagnosis, postpone effective treatment, or impair anti-lymphoma activity of rituximab. 相似文献954.
The ribosomal DNA (rDNA) genes of Saccharomyces cerevisiae are located in a tandem array of about 150 repeats. Using a diploid with markers flanking and within the rDNA array, we showed that low levels of DNA polymerase alpha elevate recombination between both homologues and sister chromatids, about five-fold in mitotic cells and 30-fold in meiotic cells. This stimulation is independent of Fob1p, a protein required for the programmed replication fork block (RFB) in the rDNA. We observed that the fob1 mutation alone significantly increased meiotic, but not mitotic, rDNA recombination, suggesting a meiosis-specific role for this protein. We found that meiotic cells with low polymerase alpha had decreased Sir2p binding and increased Spo11p-catalyzed double-strand DNA breaks in the rDNA. Furthermore, meiotic crossover interference in the rDNA is absent. These results suggest that the hyper-Rec phenotypes resulting from low levels of DNA polymerase alpha in mitosis and meiosis reflect two fundamentally different mechanisms: the increased mitotic recombination is likely due to increased double-strand DNA breaks (DSBs) resulting from Fob1p-independent stalled replication forks, whereas the hyper-Rec meiotic phenotype results from increased levels of Spo11-catalyzed DSBs in the rDNA. 相似文献
955.
Embryo quality related to its developmental potential is now one of the most important issues in modern embryology. It has been demonstrated that some in vitro produced blastocysts fail to hatch and implant after transfer despite a normal morphology. Although embryos are able to adjust to sub-optimal culture conditions, significant changes in expression profiles of developmentally important genes have been noticed. Timing of the first zygotic cleavage is considered a non-invasive marker of embryo developmental potential and has been successfully used in human IVF programs for identifying embryos of superior quality. Early-cleaving zygotes are more likely to develop to the blastocyst stage than their late-cleaving counterparts. The timing of the first zygotic cleavage has been associated with several parameters that may affect developmental potential of the resulting embryos. The mechanism causing variation in the timing of the first zygotic cleavage has not been identified. It may be related to culture environment or to some intrinsic factors within the oocyte, the sperm or both. In this paper we discuss some of the important aspects related to the timing of the first zygotic cleavage and its influence on the developmental competence of resulting embryos. 相似文献
956.
New properties of mitochondrial ATP-regulated potassium channels 总被引:1,自引:0,他引:1
The ATP-regulated potassium channel is present in the inner membrane of heart mitochondria. In this study, the activity of
a single channel was measured after reconstituting the myocardium inner mitochondrial membrane into a planar lipid bilayer.
We provide direct evidence of vectorial pH regulation of mitoKATP channels. When the matrix side was alkalized, this changed the channel conductance, the open probability, and the mean open
and closed dwell time distributions. The conductance of the mitoKATP channel increased from about 110 ± 8 to 145 ± 5 pS upon changing the pH from 7.2 to 8.2. This effect was reversed by reverting
the pH to the neutral value. The mitoKATP channel activity was not altered by alkalization of the cytosolic side of the planar lipid bilayer. We also observed that
acidification from pH 7.2 to 6.2, in either the matrix or cytosolic compartments, decreased the open probability of the channel.
This effect was reversed by perfusion with a pH 7.2 medium. Additionally, our results suggest that the mitoKATP channel is regulated by multiple phosphorylation events. The channel activity was inhibited by an ATP/Mg2+ complex, but not by ATP alone, nor by a non-hydrolysable ATP analog, e.g. AMP-PNP/Mg2+. The mitoKATP channel “run-down” was reversed by incubating with the ATP/Mg2+ complex on both sides of the planar lipid bilayer. We conclude that both pH and ATP play an important regulatory role for
the cardiac mitoKATP channel with respect to the phenomenon of ischemia–reperfusion. 相似文献
957.
To evaluate the acclimative ability of current-year and previous-year needles of a shade tolerant conifer Taxus baccata L. to contrasting irradiance conditions, seedlings were raised under 27% solar irradiance and at 3 years of age they were
transferred to an experimental garden and grown for one season under full irradiance (HL), 18% irradiance (ML) or 5% irradiance
(LL). Whereas previous year needles did not change anatomically, current year needles in HL were thicker and had a thicker
palisade and spongy mesophyll, and greater leaf mass per area than ML or LL needles. LL needles had greater nitrogen concentration
than HL needles irrespective of age but only previous year LL needles also had an increased N per area content, thanks to
their lack of reduction in LMA. Adjustment of chlorophyll and carotenoid content occurred in both needle age classes with
LL and ML needles having much higher concentrations but, in current year needles, only slightly higher per area content than
HL needles. Chlorophyll a/b ratio was not affected by age or irradiance. These modifications had no significant effect on photosynthetic capacities,
which did not significantly differ between the age classes in HL or LL treatment and between treatments. On the other hand,
high growth irradiance resulted in a greater photochemical yield, photochemical quenching, apparent electron transport rate
and inducible non-photochemical quenching in needles formed in the current season. In previous year needles, however, only
inducible NPQ was enhanced by high irradiance with other parameters remaining identical among treatments. To test sensitivity
to photoinhibition, at the end of the summer plants from the three irradiance levels were transferred to a HL situation and
F
v/F
M was determined over the following 18 days. Sensitivity to photoinhibition was negatively related to growth irradiance and
previous year needles were less photoinhibited than current year needles. Thus, differences in acclimation ability between
needle age classes were most pronounced at the level of anatomy and light reactions of photosynthesis, both of which showed
almost no plasticity in previous year needles but were considerably modified by irradiance in current year needles. 相似文献
958.
Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal. 相似文献
959.
1‐Aminobenzocyclobutene‐1‐phosphonic Acid and Related Compounds as Inhibitors of Phenylalanine Ammonia‐Lyase
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Five new geminal aminocycloalkanephosphonic acids ( 4 – 8 ) containing both an aromatic ring and a cycloalkane ring were synthesized and evaluated as potential inhibitors of buckwheat phenylalanine ammonia‐lyase (PAL). Within the set of compounds which are related to 2‐aminoindane‐2‐phosphonic acid (AIP, 3 ), a known powerful inhibitor of PAL, racemic 1‐aminobenzocyclobutene‐1‐phosphonic acid ( 4 ), was six times weaker than AIP as an in vitro inhibitor of buckwheat PAL, but six times stronger than AIP as an in vivo inhibitor of phenylalanine‐derived anthocyanin synthesis in buckwheat. 相似文献
960.
Piotr Minias Linda A. Whittingham Peter O. Dunn 《Evolution; international journal of organic evolution》2017,71(2):432-441
The major histocompatibility complex (MHC) plays a key role in pathogen recognition as a part of the vertebrate adaptive immune system. The great diversity of MHC genes in natural populations is maintained by different forms of balancing selection and its strength should correlate with the diversity of pathogens to which a population is exposed and the rate of exposure. Despite this prediction, little is known about how life‐history characteristics affect selection at the MHC. Here, we examined whether the strength of balancing selection on MHC class II genes in birds (as measured with nonsynonymous nucleotide substitutions, dN) was related to their social or migratory behavior, two life‐history characteristics correlated with pathogen exposure. Our comparative analysis indicated that the rate of nonsynonymous substitutions was higher in colonial and migratory species than solitary and resident species, suggesting that the strength of balancing selection increases with coloniality and migratory status. These patterns could be attributed to: (1) elevated transmission rates of pathogens in species that breed in dense aggregations, or (2) exposure to a more diverse fauna of pathogens and parasites in migratory species. Our study suggests that differences in social structure and basic ecological traits influence MHC diversity in natural vertebrate populations. 相似文献