全文获取类型
收费全文 | 5431篇 |
免费 | 424篇 |
国内免费 | 274篇 |
专业分类
6129篇 |
出版年
2024年 | 6篇 |
2023年 | 62篇 |
2022年 | 141篇 |
2021年 | 253篇 |
2020年 | 175篇 |
2019年 | 207篇 |
2018年 | 188篇 |
2017年 | 135篇 |
2016年 | 211篇 |
2015年 | 341篇 |
2014年 | 384篇 |
2013年 | 414篇 |
2012年 | 504篇 |
2011年 | 443篇 |
2010年 | 270篇 |
2009年 | 243篇 |
2008年 | 267篇 |
2007年 | 242篇 |
2006年 | 189篇 |
2005年 | 177篇 |
2004年 | 167篇 |
2003年 | 120篇 |
2002年 | 108篇 |
2001年 | 106篇 |
2000年 | 93篇 |
1999年 | 99篇 |
1998年 | 40篇 |
1997年 | 51篇 |
1996年 | 41篇 |
1995年 | 38篇 |
1994年 | 29篇 |
1993年 | 33篇 |
1992年 | 41篇 |
1991年 | 37篇 |
1990年 | 46篇 |
1989年 | 36篇 |
1988年 | 23篇 |
1987年 | 24篇 |
1986年 | 13篇 |
1985年 | 14篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1979年 | 14篇 |
1978年 | 8篇 |
1973年 | 9篇 |
1972年 | 6篇 |
1971年 | 9篇 |
1968年 | 5篇 |
排序方式: 共有6129条查询结果,搜索用时 15 毫秒
151.
Wan-Jin Liao Yi Hu Bi-Ru Zhu Xia-Qing Zhao Yan-Fei Zeng Da-Yong Zhang 《Annals of botany》2009,104(7):1405-1412
Background and Aims
Reduction in female fitness in large clones can occur as a result of increased geitonogamous self-fertilization and its influence through inbreeding depression. This possibility was investigated in the self-compatible, bee-pollinated perennial herb Aconitum kusnezoffii which varies in clone size.Methods
Field investigations were conducted on pollinator behaviour, flowering phenology and variation in seed set. The effects of self-pollination following controlled self- and cross-pollination were also examined. Selfing rates of differently sized clones were assessed using allozyme markers.Key Results
High rates of geitonogamous pollination were associated with large display size. Female fitness at the ramet level decreased with clone size. Fruit and seed set under cross-pollination were significantly higher than those under self-pollination. The pre-dispersal inbreeding depression was estimated as 0·502 based on the difference in seed set per flower between self- and cross-pollinated flowers. Selfing rates of differently sized clones did not differ.Conclusions
It is concluded that in A. kusnezoffii the negative effects of self-pollination causing reduced female fertility with clone size arise primarily from a strong early-acting inbreeding depression leading to the abortion of selfed embryos prior to seed maturation.Key words: Early-acting inbreeding depression, Aconitum kusnezoffii, clone size, female reproductive success, geitonogamy 相似文献152.
Runhua Liao Yan Li Zhu Wang Yu Miao Ke Shen Peng Shi Yan Ma Wentao Li Ai-Min Li 《Biotechnology and Bioprocess Engineering》2014,19(1):183-190
The treatment of high-salinity, high-nitrate wastewater was investigated in a single expanded granular sludge bed reactor. Complete denitrification was achieved when nitrate concentration was as high as 6,000 mg N/L and the salinity of influent reached 11% NaCl at liquid up-flow velocity of 3.0 m/h, hydraulic retention time of, 24 h and the C/N molar ratio of 2.0. Furthermore, 454-pyrosequencing technology was used to analyze archaea bacterial diversity under high salinity and high nitrate conditions. Results showed that the total number of effective sequences was 5749 consisting of 5678 bacterial sequences and 71 archaea sequences after denoising and filtering out chimeras, which could be affiliated to 5 phylogenetic groups, including Proteobacteria, Firmicutes, Euryarchaeota, Crenarchaeota and unclassified phylum. Although Proteobacteria was the dominant microbial population, two archaea phylogenetic groups-Crenarchaeota and Euryarchaeota were observed in this study. 相似文献
153.
Mani SA Guo W Liao MJ Eaton EN Ayyanan A Zhou AY Brooks M Reinhard F Zhang CC Shipitsin M Campbell LL Polyak K Brisken C Yang J Weinberg RA 《Cell》2008,133(4):704-715
The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties. 相似文献
154.
D Liao J J Martin de Llano J P Himanen J M Manning F A Ferrone 《Biophysical journal》1996,70(5):2442-2447
We have developed a photolytic method to determine the concentration of reactive hemes in a solution in the presence of a trace amount of CO. By measurement of the bimolecular rate of CO binding, and by calibration of the rate constant under equivalent conditions, the concentration of the reactive hemes can be determined. In a solution of sickle hemoglobin, the molecules in the gel contribute negligibly to the recombination rate, allowing the concentration of the molecules in the solution phase to be determined. To optimize signal to noise, modulated excitation methods were employed, although the method could also be used with pulse techniques and suitable signal averaging. Because the optical method employs a microspectrophotometer, only a few microliters of concentrated Hb solution is required to reproduce the entire temperature dependence of the solubility previously determined by centrifugation using milliliter quantities of solutions of the same concentration. This should be especially useful for studies of site-directed mutants, and we present results obtained on one such HbS in which Leu 88 beta has been replaced by Ala. The free energy difference in the polymerization of the Leu 88 beta double mutant is consistent with known differences in the amino acid hydrophobicities. The calibration required for these experiments also provides an excellent determination of the activation energy for binding the first CO to deoxy Hb. 相似文献
155.
156.
T cell immunoglobulin and mucin domain (Tim)-3 is expressed on activated CD4+ and CD8+ T cells. Identification of galectin-9 as a ligand for Tim-3 has now firmly established the Tim-3/galectin-9 pathway, which results in apoptosis of effector CD4+ and CD8+ T cells. Moreover, Th17 cells are a recently discovered CD4+ effector T cell, which are important in antimicrobial immunity. Whether the Tim-3/galectin-9 pathway affects Th17 immunity has not been elucidated. Here, we demonstrated expression of Tim-3 on Th17 cells by flow cytometry. Th17-skewed cells were sensitive to galectin-9-induced apoptosis. In vitro administration of galectin-9 decreased stimulated Th17 cells and inhibited production of IL-17. Interestingly, Klebsiella pneumoniae (K. pneumoniae) infection led to enhanced IL-17 levels. Recombinant galectin-9 significantly decreased IL-17 in vivo, which resulted in reduced bacterial clearance and high mortality. These observations suggest that the Tim-3/galectin-9 pathway plays an important role in termination of Th17-immune responses, and could be a therapeutic target for inflammatory diseases. 相似文献
157.
Nikrodhanond AA Ortiga-Carvalho TM Shibusawa N Hashimoto K Liao XH Refetoff S Yamada M Mori M Wondisford FE 《The Journal of biological chemistry》2006,281(8):5000-5007
Hypothalamic thyrotropin-releasing hormone (TRH) stimulates thyroid-stimulating hormone (TSH) secretion from the anterior pituitary. TSH then initiates thyroid hormone (TH) synthesis and release from the thyroid gland. Although opposing TRH and TH inputs regulate the hypothalamic-pituitary-thyroid axis, TH negative feedback is thought to be the primary regulator. This hypothesis, however, has yet to be proven in vivo. To elucidate the relative importance of TRH and TH in regulating the hypothalamic-pituitary-thyroid axis, we have generated mice that lack either TRH, the beta isoforms of TH receptors (TRbeta KO), or both (double KO). TRbeta knock-out (KO) mice have significantly higher TH and TSH levels compared with wild-type mice, in contrast to double KO mice, which have reduced TH and TSH levels. Unexpectedly, hypothyroid double KO mice also failed to mount a significant rise in serum TSH levels, and pituitary TSH immunostaining was markedly reduced compared with all other hypothyroid mouse genotypes. This impaired TSH response, however, was not due to a reduced number of pituitary thyrotrophs because thyrotroph cell number, as assessed by counting TSH immunopositive cells, was restored after chronic TRH treatment. Thus, TRH is absolutely required for both TSH and TH synthesis but is not necessary for thyrotroph cell development. 相似文献
158.
In order to investigate the possible involvement of corticotropin-releasing factor (CRF) and somatostatin (SRIF) on thyrotropin-releasing hormone (TRH) neuronal cell activity in the rat hypothalamic paraventricular nucleus, we have proceeded to the simultaneous localization of CRF or SRIF and TRH. For this purpose, we used a dual immunostaining procedure that employed antibodies to CRF and SRIF and peroxidase-labeled goat anti-rabbit IgG as a first sequence, and antibodies to a cryptic fragment (Phe178-Glu199) of pro-TRH (to label TRH neurons) and alkaline phosphatase-labeled goat anti-rabbit IgG as the second sequence. A rich innervation of the paraventricular nucleus by immunoreactive CRF and SRIF fibers was observed. A large number of CRF and SRIF nerve endings were seen intimate anatomic proximity and often appeared to surround TRH-containing cell bodies. These results strongly suggest that TRH neurons might be regulated by both CRF and SRIF. These interactions might be the neuroanatomical basis for the already observed inhibitory effects of CRF and SRIF on TRH release. 相似文献
159.
Zhandi Liao Dean Lockhead Joshua R. St. Clair Eric D. Larson Courtney E. Wilson Catherine Proenza 《The Journal of general physiology》2012,140(5):557-566
Hyperpolarization-activated, cyclic nucleotide–sensitive (HCN) channels produce the If and Ih currents, which are critical for cardiac pacemaking and neuronal excitability, respectively. HCN channels are modulated by cyclic AMP (cAMP), which binds to a conserved cyclic nucleotide–binding domain (CNBD) in the C terminus. The unliganded CNBD has been shown to inhibit voltage-dependent gating of HCNs, and cAMP binding relieves this “autoinhibition,” causing a depolarizing shift in the voltage dependence of activation. Here we report that relief of autoinhibition can occur in the absence of cAMP in a cellular context- and isoform-dependent manner: when the HCN4 isoform was expressed in Chinese hamster ovary (CHO) cells, the basal voltage dependence was already shifted to more depolarized potentials and cAMP had no further effect on channel activation. This “pre-relief” of autoinhibition was specific both to HCN4 and to CHO cells; cAMP shifted the voltage dependence of HCN2 in CHO cells and of HCN4 in human embryonic kidney (HEK) cells. The pre-relief phenotype did not result from different concentrations of soluble intracellular factors in CHO and HEK cells, as it persisted in excised cell-free patches. Likewise, it did not arise from a failure of cAMP to bind to the CNBD of HCN4 in CHOs, as indicated by cAMP-dependent slowing of deactivation. Instead, a unique ∼300–amino acid region of the distal C terminus of HCN4 (residues 719–1012, downstream of the CNBD) was found to be necessary, but not sufficient, for the depolarized basal voltage dependence and cAMP insensitivity of HCN4 in CHO cells. Collectively, these data suggest a model in which multiple HCN4 channel domains conspire with membrane-associated intracellular factors in CHO cells to relieve autoinhibition in HCN4 channels in the absence of cAMP. These findings raise the possibility that such ligand-independent regulation could tune the activity of HCN channels and other CNBD-containing proteins in many physiological systems. 相似文献
160.
SP Yeh YM Liao WJ Lo CL Lin LY Bai CY Lin CY Hsieh YC Chang YT Huang CF Chiu 《PloS one》2012,7(9):e44416