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排序方式: 共有524条查询结果,搜索用时 31 毫秒
51.
52.
Tandon VK Yadav DB Chaturvedi AK Shukla PK 《Bioorganic & medicinal chemistry letters》2005,15(13):3288-3291
A series of (1,4)-naphthoquinono [3,2-c]-1H-pyrazoles and their (1,4)-naphthohydroquinone derivatives 2-7 were synthesized and evaluated for antifungal, antibacterial, and anticancer activities. The structure-activity relationship of these compounds was studied and the results show that the compound 2b exhibited in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, and also possessed antibacterial profile against Klebsiella pneumoniae and Escherichia coli whereas 1c showed anticancer activity against Walker 256 Carcinosarcoma in rats. 相似文献
53.
54.
Shrivastava A Tiwari M Sinha RA Kumar A Balapure AK Bajpai VK Sharma R Mitra K Tandon A Godbole MM 《The Journal of biological chemistry》2006,281(28):19762-19771
Molecular iodine (I2) is known to inhibit the induction and promotion of N-methyl-n-nitrosourea-induced mammary carcinogenesis, to regress 7,12-dimethylbenz(a)anthracene-induced breast tumors in rat, and has also been shown to have beneficial effects in fibrocystic human breast disease. Cytotoxicity of iodine on cultured human breast cancer cell lines, namely MCF-7, MDA-MB-231, MDA-MB-453, ZR-75-1, and T-47D, is reported in this communication. Iodine induced apoptosis in all of the cell lines tested, except MDA-MB-231, shown by sub-G1 peak analysis using flow cytometry. Iodine inhibited proliferation of normal human peripheral blood mononuclear cells; however, it did not induce apoptosis in these cells. The iodine-induced apoptotic mechanism was studied in MCF-7 cells. DNA fragmentation analysis confirmed internucleosomal DNA degradation. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling established that iodine induced apoptosis in a time- and dose-dependent manner in MCF-7 cells. Iodine-induced apoptosis was independent of caspases. Iodine dissipated mitochondrial membrane potential, exhibited antioxidant activity, and caused depletion in total cellular thiol content. Western blot results showed a decrease in Bcl-2 and up-regulation of Bax. Immunofluorescence studies confirmed the activation and mitochondrial membrane localization of Bax. Ectopic Bcl-2 overexpression did not rescue iodine-induced cell death. Iodine treatment induces the translocation of apoptosis-inducing factor from mitochondria to the nucleus, and treatment of N-acetyl-L-cysteine prior to iodine exposure restored basal thiol content, ROS levels, and completely inhibited nuclear translocation of apoptosis-inducing factor and subsequently cell death, indicating that thiol depletion may play an important role in iodine-induced cell death. These results demonstrate that iodine treatment activates a caspase-independent and mitochondria-mediated apoptotic pathway. 相似文献
55.
Pineda-Alvarez DE Roessler E Hu P Srivastava K Solomon BD Siple CE Fan CM Muenke M 《Human genetics》2012,131(2):301-310
Holprosencephaly (HPE) is the most common disorder of the developing forebrain in humans, and is characterized by varying
degrees of abnormal union of the cerebral hemispheres. These defects are typically co-associated with midline craniofacial
anomalies. The combination of forebrain and craniofacial defects that comprise HPE can present along a broad and variable
phenotypic spectrum. Both the SHH and NODAL signaling pathways play important roles in the pathogenesis of this disorder.
Disruption of these pathways by chromosomal rearrangements, mutations in pathway-related genes and/or biochemical alterations
are proposed to contribute to HPE in a large number of patients. Additional factors that are not yet fully delineated are
also very likely to be involved in the pathogenesis and phenotypic heterogeneity of the disorder. Genetic loss of GAS1, a cell membrane receptor and positive regulator of SHH, has been demonstrated to contribute to the HPE phenotypic spectrum
in animal models. We have evaluated the coding and flanking sequence of GAS1 in 394 patients who have clinical findings within the HPE phenotypic spectrum, and now report five novel missense sequence
variants among five unrelated HPE probands. Finally, we tested the effect of these variants (as well as previously reported
GAS1 variants) on the ability of GAS1 to bind to SHH. Here, we demonstrate that sequence variants in GAS1 can impair its physical
interaction with SHH, suggesting a decrease in the SHH downstream signaling cascade as a pathogenic mechanism of disease. 相似文献
56.
57.
The majority of microRNAs detectable in serum and saliva is concentrated in exosomes 总被引:1,自引:0,他引:1
There is an increasing interest in using microRNAs (miRNA) as biomarkers in autoimmune diseases. They are easily accessible in many body fluids but it is controversial if they are circulating freely or are encapsulated in microvesicles, particularly exosomes. We investigated if the majority of miRNas in serum and saliva are free-circulating or concentrated in exosomes. Exosomes were isolated by ultracentrifugation from fresh and frozen human serum and saliva. The amount of selected miRNAs extracted from the exosomal pellet and the exosome-depleted serum and saliva was compared by quantitative RT-PCR. Some miRNAs tested are ubiquitously expressed, others were previously reported as biomarkers. We included miRNAs previously reported to be free circulating and some thought to be exosome specific. The purity of exosome fraction was confirmed by electronmicroscopy and western blot. The concentration of miRNAs was consistently higher in the exosome pellet compared to the exosome-depleted supernatant. We obtained the same results using an equal volume or equal amount of total RNA as input of the RT-qPCR. The concentration of miRNA in whole, unfractionated serum, was between the exosomal pellet and the exosome-depleted supernatant. Selected miRNAs, which were detectable in exosomes, were undetectable in whole serum and the exosome-depleted supernantant. Exosome isolation improves the sensitivity of miRNA amplification from human biologic fluids. Exosomal miRNA should be the starting point for early biomarker studies to reduce the probability of false negative results involving low abundance miRNAs that may be missed by using unfractionated serum or saliva. 相似文献
58.
Ravi Tandon Maria T. M. Giret Devi SenGupta Vanessa A. York Andrew A. Wiznia Michael G. Rosenberg Esper G. Kallas Lishomwa C. Ndhlovu Douglas F. Nixon 《PloS one》2012,7(9)
As perinatally HIV-1-infected children grow into adolescents and young adults, they are increasingly burdened with the long-term consequences of chronic HIV-1 infection, with long-term morbidity due to inadequate immunity. In progressive HIV-1 infection in horizontally infected adults, inflammation, T cell activation, and perturbed T cell differentiation lead to an “immune exhaustion”, with decline in T cell effector functions. T effector cells develop an increased expression of CD57 and loss of CD28, with an increase in co-inhibitory receptors such as PD-1 and Tim-3. Very little is known about HIV-1 induced T cell dysfunction in vertical infection. In two perinatally antiretroviral drug treated HIV-1-infected groups with median ages of 11.2 yr and 18.5 yr, matched for viral load, we found no difference in the proportion of senescent CD28−CD57+CD8+ T cells between the groups. However, the frequency of Tim-3+CD8+ and Tim-3+CD4+ exhausted T cells, but not PD-1+ T cells, was significantly increased in the adolescents with longer duration of infection compared to the children with shorter duration of HIV-1 infection. PD-1+CD8+ T cells were directly associated with T cell immune activation in children. The frequency of Tim-3+CD8+ T cells positively correlated with HIV-1 plasma viral load in the adolescents but not in the children. These data suggest that Tim-3 upregulation was driven by both HIV-1 viral replication and increased age, whereas PD-1 expression is associated with immune activation. These findings also suggest that the Tim-3 immune exhaustion phenotype rather than PD-1 or senescent cells plays an important role in age-related T cell dysfunction in perinatal HIV-1 infection. Targeting Tim-3 may serve as a novel therapeutic approach to improve immune control of virus replication and mitigate age related T cell exhaustion. 相似文献
59.
CE Ormsby D Sengupta R Tandon SG Deeks JN Martin RB Jones MA Ostrowski KE Garrison JA Vázquez-Pérez G Reyes-Terán DF Nixon 《PloS one》2012,7(8):e41021
Human endogenous retroviruses (HERV) are remnants of ancestral retroviral infections integrated into the germ line, and constitute approximately 8% of the genome. Several autoimmune disorders, malignancies, and infectious diseases such as HIV-1 are associated with higher HERV expression. The degree to which HERV expression in vivo results in persistent inflammation is not known. We studied the association of immune activation and HERV-K expression in 20 subjects with chronic, untreated progressive HIV-1 infection and 10 HIV-1 negative controls. The mean HERV-K gag and env RNA expression level in the HIV-1 infected cohort was higher than in the control group (p = 0.0003), and was negatively correlated with the frequency of activated CD38+HLA-DR+CD4+ T cells (Rho = −0.61; p = 0.01) and activated CD38+HLA-DR+CD8+ T cells (Rho = −0.51; p = 0.03). Although HIV-infected persons had higher levels of HERV-K RNA expression (as expected), the level of RNA expression was negatively associated with level of T cell activation. The mechanism for this unexpected association remains to be defined. 相似文献
60.
Mitsuteru Suzuki Pramod Tandon Masaya Ishikawa Takayuki Toyomasu 《Plant biotechnology reports》2008,2(2):123-131
Vitrification methods are convenient for cryopreserving plant specimens, as the specimens are plunged directly into liquid
nitrogen (LN) from ambient temperatures. However, tissues and species with poor survival are still not uncommon. The development
of vitrification solutions with high survival that cover a range of materials is important. We attempted to develop new vitrification
solutions using bromegrass cells and found that VSL, comprising 20% (w/v) glycerol, 30% (w/v) ethylene glycol, 5% (w/v) sucrose,
10% (w/v) DMSO and 10 mM CaCl2, gave the highest survival following cryopreservation, as determined by fluorescein diacetate staining. However, the cryopreserved
cells showed little regrowth, for unknown reasons. To check its applicability, VSL was used to cryopreserve gentian axillary
buds and the performance was compared with those of conventional vitrification solutions. Excised gentian stem segments with
axillary buds (shoot apices) were two-step precultured with sucrose to induce osmotic tolerance prior to cryopreservation.
Gentian axillary buds cryopreserved using VSL following the appropriate preculturing approach exhibited 78% survival (determined
by the regrowth capacity), which was comparable to PVS2 and PVS1 and far better than PVS3. VSL had a wider optimal incubation
time (20–45 min) than PVS2 and was more suitable for cryopreserving gentian buds. The optimal duration of the first step of
the preculture was 7–11 days, and preculturing with sucrose and glucose gave a much higher survival than fructose and maltose.
VSL was able to vitrify during cooling to LN temperatures, as glass transition and devitrification points were detected in
the warming profiles from differential scanning calorimetry. VSL and its derivative, VSL+, seem to have the potential to be
good alternatives to PVS2 for the cryopreservation of some materials, as exemplified by gentian buds.
Mitsuteru Suzuki, Pramod Tandon and Masaya Ishikawa contributed equally to the work. 相似文献