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121.
Tatham MH Geoffroy MC Shen L Plechanovova A Hattersley N Jaffray EG Palvimo JJ Hay RT 《Nature cell biology》2008,10(5):538-546
In acute promyelocytic leukaemia (APL), the promyelocytic leukaemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). This disease can be treated effectively with arsenic, which induces PML modification by small ubiquitin-like modifiers (SUMO) and proteasomal degradation. Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (also known as SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro. In the absence of RNF4, arsenic failed to induce degradation of PML and SUMO-modified PML accumulated in the nucleus. These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis. 相似文献
122.
Kowalczyk AE Kaczmarek MM Schams D Ziecik AJ 《Molecular reproduction and development》2008,75(10):1558-1566
The purpose of the present study was to investigate the effects of prostaglandin (PG) E(2) and tumor necrosis factor (TNF) alpha on expression of vascular endothelial growth factor (VEGF) and its receptors, fms-like tyrosine kinase (Flt-1) and fetal liver kinase-1/kinase insert domain-containing receptor (Flk-1/KDR), in cultured porcine luteal cells. Real-time PCR was used for quantification of VEGF and its receptors mRNA, whereas VEGF release by luteal cells was determined by radioimmunoassay (RIA). Only the highest dose of PGE(2) (1 microM) after 6 hr of incubation stimulated VEGF release by luteal cells collected in the mid-luteal phase (P < 0.05). Moreover, PGE(2) (100 nM, 1 microM) significantly stimulated VEGF secretion by luteal cells in the late phase and during pregnancy on Days 10-12 (P < 0.05). Elevated mRNA expression of both VEGF 120 and VEGF 164 isoforms was found in luteal cells cultured with PGE(2). The lack of an effect of PGE(2) on VEGF receptors mRNA expression was observed. TNFalpha was able to significantly stimulate VEGF release from cells obtained in the mid- and late luteal phase or during early pregnancy. All tested doses enhanced mRNA levels of VEGF 120 isoform, but not VEGF 164. Additionally, TNFalpha was able to decrease Flk-1/KDR mRNA expression, whereas Flt-1 mRNA levels were not affected. These results indicated that PGE(2) and TNFalpha influenced VEGF ligand-receptor system expression in porcine luteal cells and may therefore play an important role in regulation of luteal functions during the estrous cycle and pregnancy in pigs. 相似文献
123.
Pietri Puustinen Anna Rytter Monika Mortensen Pekka Kohonen José M. Moreira Marja J??ttel? 《The Journal of cell biology》2014,204(5):713-727
mTORC1 (mammalian target of rapamycin complex 1) integrates information regarding availability of nutrients and energy to coordinate protein synthesis and autophagy. Using ribonucleic acid interference screens for autophagy-regulating phosphatases in human breast cancer cells, we identify CIP2A (cancerous inhibitor of PP2A [protein phosphatase 2A]) as a key modulator of mTORC1 and autophagy. CIP2A associates with mTORC1 and acts as an allosteric inhibitor of mTORC1-associated PP2A, thereby enhancing mTORC1-dependent growth signaling and inhibiting autophagy. This regulatory circuit is reversed by ubiquitination and p62/SQSTM1-dependent autophagic degradation of CIP2A and subsequent inhibition of mTORC1 activity. Consistent with CIP2A’s reported ability to protect c-Myc against proteasome-mediated degradation, autophagic degradation of CIP2A upon mTORC1 inhibition leads to destabilization of c-Myc. These data characterize CIP2A as a distinct regulator of mTORC1 and reveals mTORC1-dependent control of CIP2A degradation as a mechanism that links mTORC1 activity with c-Myc stability to coordinate cellular metabolism, growth, and proliferation. 相似文献
124.
The cucumber cotyledon expansion test was used as a model system to study a possible relationship between cytokinin and polyamines.
When kinetin was applied to excised cotyledons incubated in the dark it caused a marked increase in the activity of arginine
decarboxylase. As a result of ADC action, putrescine content also rose markedly, whereas the level of spermidine and spermine
decreased. However, inhibition of putrescine biosynthesis with D-arginine did not affect cytokinin promotion growth. Applied
alone, putrescine had no significant effect on growth. These results indicate that the large increase in putrescine content
that derives from cytokinin treatment cotyledons is not essential for cytokinin-induced expansion of cotyledons. Addition
of K+ and Ca2+ ions to the cotyledons incubated with cytokinin caused a marked reduction in the putrescine level and ADC activity.
The higher level of putrescine (35 %) and spermine (62 %) bound to chromatin and the large increase (174 %) in spermidine
content bound to ribosomes which derive from cytokinintreated cotyledons in relation to literature data can indicate that
these polyamines may play an important role in gene expression during cytokinin-stimulated expansion of cucumber cotyledons.
The inhibition of cytokinin effect, viz. enlargement of the cotyledons by inhibitors of spermidine biosynthesis, additionally suggessted a possible involvement of
polyamines in cytokinin action. 相似文献
125.
Implication of tissue transglutaminase and desmoplakin in cell adhesion mechanism in human epidermis
Esposito C Lombardi ML Ruocco V Cozzolino A Mariniello L Porta R 《Molecular and cellular biochemistry》2000,206(1-2):57-65
The distribution patterns of both tissue and keratinocyte transglutaminases (TGase), as well as that of desmoplakin (DP), have been immunohistochemically investigated in human skin cultured in the absence or presence of cystamine and enalapril, two acantholytic agents. In the control samples, tissue TGase is predominantly expressed in lower layers of the epidermis and is located intercellularly. Conversely, in tissues cultured with cystamine or enalapril, a diffuse cytoplasmatic staining was observed. Similarly, DP, detected on the cell membrane in the control, shifts into the cytosol of the keratinocytes following treatment. The distribution pattern of the keratinocyte enzyme in the acantholytic epidermis was identical to that observed in the normal one. Since cystamine and enalapril are TGase inhibitors and DP was shown to act as a TGase substrate in vitro, we suggest that DP and tissue enzyme may participate in cell adhesion at the intraepidermal level. 相似文献
126.
Anatomical study of zygotic and somatic embryos of Tilia cordata 总被引:1,自引:0,他引:1
A comparative anatomical study was carried out on zygotic and somatic embryos of Tilia cordata Mill. to evaluate the effect of growth conditions on their development. Zygotic embryos (heart-shaped, torpedo, cotyledonary),
collected during two autumn periods, were examined to investigate the effect of growing season on embryo development. In comparison,
the influence of growth conditions on the development of somatic embryos in vitro was also studied. Treatment with abscisic acid (ABA) and polyethylene glycol-4000 induced the development of somatic cotyledonary
embryos similar to zygotic embryos with respect to morphology and anatomy, as illustrated by the differentiation of the apical
meristems and of the procambium. The pattern of accumulation of starch and protein was also similar in these embryos. Somatic
cotyledonary embryos that developed spontaneously without ABA showed defective accumulation of storage material and a general
failure to form the shoot apical meristem, leading to very low germination rates. Vacuolar phenolic deposits were observed
along the procambium of both zygotic and somatic embryos regardless of the maturation stage. Tracheid formation was observed
only in somatic embryos formed without ABA in the medium and in precociously germinated somatic embryos. Phenolic vacuolar
inclusions were frequently observed in epidermal cells of these embryos.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
127.
128.
Ana Maria Fernandez-Pujals Mark James Adams Pippa Thomson Andrew G. McKechanie Douglas H. R. Blackwood Blair H. Smith Anna F. Dominiczak Andrew D. Morris Keith Matthews Archie Campbell Pamela Linksted Chris S. Haley Ian J. Deary David J. Porteous Donald J. MacIntyre Andrew M. McIntosh 《PloS one》2015,10(11)
The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD. 相似文献
129.
130.
Li L Stillemark-Billton P Beck C Boström P Andersson L Rutberg M Ericsson J Magnusson B Marchesan D Ljungberg A Borén J Olofsson SO 《Journal of lipid research》2006,47(1):67-77
Epigallocatechin gallate (EGCG) increases the formation of cytosolic lipid droplets by a mechanism that is independent of the rate of triglyceride biosynthesis and involves an enhanced fusion between lipid droplets, a process that is crucial for their growth in size. EGCG treatment reduced the secretion of both triglycerides and apolipoprotein B-100 (apoB-100) VLDLs but not of transferrin, albumin, or total proteins, indicating that EGCG diverts triglycerides from VLDL assembly to storage in the cytosol. This is further supported by the observed increase in both intracellular degradation of apoB-100 and ubiquitination of the protein (indicative of increased proteasomal degradation) in EGCG-treated cells. EGCG did not interfere with the microsomal triglyceride transfer protein, and the effect of EGCG on the secretion of VLDLs was found to be independent of the LDL receptor. Thus, our results indicate that EGCG promotes the accumulation of triglycerides in cytosolic lipid droplets, thereby diverting lipids from the assembly of VLDL to storage in the cytosol. Our results also indicate that the accumulation of lipids in the cytosol is not always associated with increased secretion of VLDL. 相似文献