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141.
Objectives: Proliferating cell nuclear antigen (PCNA) has often been used as a marker to aid assessment of tumour growth fraction. This paper addresses the question of whether it can be used as an S‐phase marker, when the non‐chromatin‐bound form of the protein is removed by pepsin treatment. Materials and methods: Cytofluorometric measurements were carried out after immunofluorescence staining of PCNA and counterstaining of DNA. S‐phase fraction was determined with the help of windows on PCNA versus DNA scattergrams, or mathematically from DNA histograms. Results: S‐phase fractions obtained using the two methods correlated well, but did not always agree, exact discrepancies depending on the mathematical model used for histogram analysis. Conclusions: Determination of S‐phase fractions with the help of PCNA immunofluorescence staining is possible, and probably more reliable than calculation of S‐fractions from DNA histograms. It thus offers an alternative to assays involving BrdU labelling in vivo. 相似文献
142.
Supratim Basu Aryadeep Roychoudhury Progya Paromita Saha Dibyendu N. Sengupta 《Acta Physiologiae Plantarum》2010,32(3):551-563
Extensive investigation into plant response and adaptation to diverse osmotic stresses like high salt/dehydration/low temperature,
involving a broad spectrum of cellular physiological and biochemical changes, is essential to unravel intrinsic mechanism
to mitigate against such stresses. In our previous communications, we conducted biochemical analyses of indica rice varieties,
subjected to exogenous salt/abscisic acid-mediated oxidative stress. The aim of this study was to compare differential biochemical
responses of the salt-sensitive (IR-29), salt-tolerant (Pokkali) and aromatic (Pusa Basmati or PB) rice varieties during polyethylene
glycol (PEG)-induced dehydration stress. The greater susceptibility of IR-29 and PB, to water scarcity, was reflected by the
higher toxic Na+ and putrescine accumulation, considerable decrease in (reduced/oxidized) glutathione, maximal increment in protease activity
and greater downregulation of nitrate reductase activity. On the other hand, Pokkali appeared to suffer lesser damages as
evidenced from much lower endogenous Na+ but higher K+, Ca2+ and Mg2+ accumulation, registering the highest levels of osmolytes like glycinebetaine and higher polyamines (spermidine and spermine)
accounting to improved relative water content, higher (reduced/oxidized) glutathione, maximal induction of the enzyme phenylalanine
ammonia-lyase and practically unhindered nitrate reductase activity, following PEG treatment. The highest induction of sugars
and proline in IR-29 and PB probably played the osmoprotective/antioxidative functions, enabling to a certain extent to heighten
their lipoxygenase inhibition or H2O2 scavenging potential, more than Pokkali, to ward off oxidative damages and sustain survival under critical dehydrated situations.
Thus, the salt-tolerant Pokkali also showed prominent dehydration-tolerance properties, whereas the aromatic rice PB, almost
identical in their biochemical responses to IR-29, showed greater sensitivity to PEG-mediated water deficit. 相似文献
143.
Red chili pepper (Capsicum frutescens) is a highly consumed spice throughout the world. Its principal pungent ingredient is the phenol capsaicin (8-methyl-N-vanillyl-6-nonenamide). Capsaicin causes neurogenic inflammation and has analgesic and anti-inflammatory activities. We have observed previously that dendritic cells, a key cell type in immune responses, have the receptor for capsaicin, and engagement of this receptor has powerful immune consequences. In this study, we demonstrate that intratumoral administration of capsaicin into a preexisting tumor results in retarded progression of the injected tumor regardless of whether the tumor is at its early or late stage. Furthermore, it leads to significant inhibition of growth of other, uninjected tumors in the same animal. Capsaicin-elicited immunity is shown to be T cell-mediated and tumor-specific. These results reflect the immunological potency of a neurological ligand in modulating immune response against an established tumor. 相似文献
144.
Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis 总被引:4,自引:0,他引:4
While a number of studies have documented the neurotropism of Japanese encephalitis virus (JEV), little is known regarding the molecular mechanism of neuronal death following viral infection. The tumor necrosis factor receptor (TNFR)-associated death domain (TRADD) has been suggested to be the crucial signal adaptor that mediates all intracellular responses from TNFR-1. Using mouse (Neuro2a) and human (SK-N-SH) neuroblastoma cell lines, we have shown that the altered expression of TNFR-1 and TRADD following JEV infection regulates the downstream apoptotic cascades. Activation of TRADD led to mitochondria-mediated neuronal apoptosis. As TRADD-knockout animals or deficient cell lines are unavailable, it has been difficult to definitively address the physiological role of TRADD in diseases pathology following JEV infection. We circumvented this problem by silencing TRADD expression with small-interfering RNA (siRNA) and have found that TRADD is required for TNFR-1-initiated neuronal apoptosis following in vitro infection with JEV. Interestingly, siRNA against TRADD also decreased the viral load in Neuro2a cells. Furthermore, siRNA against TRADD increased the survival of JEV-infected mice by altering the expression of pro apoptotic versus antiapoptotic molecules. These studies show that the engagement of TNFR-1 and TRADD following JEV infection plays a crucial role in neuronal apoptosis. 相似文献
145.
Sulfated homologues of heparin inhibit hepatitis C virus entry into mammalian cells 总被引:1,自引:0,他引:1
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The mechanism of entry of hepatitis C virus (HCV) through interactions between the envelope glycoproteins and specific cell surface receptors remains unclear at this time. We have previously shown with the vesicular stomatitis virus (VSV)/HCV pseudotype model that the hypervariable region 1 of the HCV E2 envelope glycoprotein helps in binding with glycosaminoglycans present on the cell surface. In this study, we have examined the binding of HCV envelope glycoproteins with chemically modified derivatives of heparin. Furthermore, we have determined the functional relevance of the interaction of heparin derivatives with HCV envelope glycoproteins for infectivity by using a human immunodeficiency virus (HIV)/HCV pseudotype, a VSV/HCV pseudotype, and cell culture-grown HCV genotype 1a. Taken together, our results suggest that the HCV envelope glycoproteins rely upon O-sulfated esters of a heparin homologue to facilitate entry into mammalian cells. 相似文献
146.
147.
Pugia MJ Jortani SA Basu M Sommer R Kuo HH Murphy S Williamson D Vranish J Boyle PJ Budzinski D Valdes R Basu SC 《Glycoconjugate journal》2007,24(1):5-15
Urinary trypsin inhibitors (uTi) suppress serine proteases during inflammation. After liberation from proinhibitors (P-alpha-I
and I-alpha-I) by the white blood cell (WBC) response, uTi readily pass through the kidneys into urine. A key uTi, bikunin,
is attached to O-linked and N-linked glycoconjugates. Recently, uTi inhibitors, called uristatins, were found to lack the
O-linked glycoconjugates. Monoclonal antibodies were produced using purified uristatin and screened for binding differences
to uristatin, bikunin, P-α-I, and I-α-I. Antibody-binding patterns were characterized using immunoaffinity binding onto protein-chip
surfaces and analysis by Surface Enhanced Laser Desorption/Ionization mass spectrometry (SELDI), using specimens from patients
and from purified uTi standards. Antibodies were developed and used in an enzyme-linked immunosorbent assay (ELISA) method
for uTi measurement in urine and plasma specimens. ELISA was performed on specimens from normal, presumed healthy, controls
and from patients who had been screened for inflammation using a high sensitivity C-reactive protein (CRP) test and a complete
blood count (CBC). Polyclonal antibody against uTi showed cross-reactivity with the Tamm–Horsfall protein (THP) and with proinhibitors.
Screening of anti-uTi monoclonal antibodies (Mab) revealed antibodies that did not cross-react with either of the above, thus
providing a tool to measure both uristatin and bikunin in urine with Mab 3G5 and in plasma with Mab 5D11. The monoclonal antibody
5D11 cross-reacts with specific N-linked glycoconjugates of uristatin present in plasma. In ca 96% of healthy adults, uTi
were present at <12 mg/l in urine and <4 mg/l in plasma. We also found that patients with an inflammation and a CRP of >2.0 mg/l
had higher urinary concentrations of uTi than the control population in every subject. Free uristatin and bikunin pass readily
into urine and are primarily bound to heavy chains that constitute the proinhibitor form in plasma. 相似文献
148.
Singh RK Indra D Mitra S Mondal RK Basu PS Roy A Roychowdhury S Panda CK 《Human genetics》2007,122(1):71-81
The aim of this study was to locate the candidate tumor suppressor genes (TSGs) loci in the chromosomal 4p15-16, 4q22-23 and
4q34-35 regions associated with the development of uterine cervical carcinoma (CA-CX). Deletion mapping of the regions by
microsatellite markers identified six discrete areas with high frequency of deletions, viz. 4p16.2 (D1: 40%), 4p15.31 (D2:
35–38%), 4p15.2 (D3: 37–40%), 4q22.2 (D4: 34%), 4q34.2-34.3 (D5: 37–59%) and 4q35.1 (D6: 40–50%). Significant correlation
was noted among the deleted regions D1, D2 and D3. The deletions in D1, D2, D5 and D6 regions are suggested to be associated
with the cervical intraepithelial neoplasia (CIN), and deletions in the D2, D3, D5 and D6 regions seems to be associated with
progression of CA-CX. The deletions in the D2 and D6 regions showed significant prognostic implications (P = 0.001; 0.02). The expression of the candidate TSG SLIT2 mapped to D2 region gradually reduced from normal cervix uteri
→CIN → CA-CX. SLIT2 promoter hypermethylation was seen in 28% CIN samples and significantly increased with tumor progression
(P = 0.04). Significant correlation was seen between SLIT2 deletion and its promoter methylation (P = 0.001), indicating that both these phenomena could occur simultaneously to inactivate this gene. Immunohistochemical analysis
showed reduced expression of SLIT2 in cervical lesions and CA-CX cell lines. Although no mutation was detected in the SLIT2
promoter region (−432 to + 55 bp), CC and AA haplotypes were seen in −227 and −195 positions, respectively. Thus, it indicates
that inactivation of SLIT2-ROBO1 signaling pathway may have an important role in CA-CX development. 相似文献
149.
Claus G. Krenn Gran Hedenstierna Samar Basu Stefan L. Marklund Josephine Hjoberg 《Nitric oxide》2007,16(4):419-424
BACKGROUND: We have previously shown that the protective effect of inhaled nitric oxide (iNO) against methacholine-induced bronchoconstriction is negated in airways subjected to hyperosmotic stress. In this study, hypothesizing that the impaired efficiency of iNO was caused by release of reactive oxygen radicals, we examined the effect of the radical scavenging enzyme superoxide dismutase (SOD). METHODS: Hemodynamic and respiratory measurements were performed on anesthetized rabbits after (1) inhalation of methacholine (MCh), (2) iNO (80ppm), followed by MCh, (3) inhalation of hypertonic saline (HS), followed by iNO and MCh and (4) pre-treatment with inhalation of SOD, followed by HS, iNO and MCh. We analyzed plasma for a marker of oxidative stress, 8-iso-prostaglandin (PG)F(2alpha) and for a marker of activation of COX-mediated inflammatory cascades, PGF(2alpha) metabolite. RESULTS: Pre-treatment with SOD restored the bronchoprotective response to iNO in hyperosmotic airways. No direct effect was seen by SOD treatment on levels of 8-iso-PGF(2alpha), but this marker of oxidative stress correlated positively with increased bronchoconstriction. Hyperosmotic challenge elevated levels of PGF(2alpha) metabolite, and pre-treatment with SOD protected against this activation of the inflammatory cascade. CONCLUSION: SOD pre-treatment restores the relaxant effects of iNO in hyperosmotically challenged airways by attenuating oxidative stress and activation of COX-mediated inflammatory cascades. 相似文献
150.
Basu S Meisert I Eggensperger E Krieger E Krenn CG 《Redox report : communications in free radical research》2007,12(4):195-202
Ischaemia-reperfusion injury resulting from interruption and restoration of blood flow might be related to free radical mediated oxidative stress and inflammation, and subsequently to post-surgery related complications. We studied the impact of renal transplantation on oxidative stress and inflammation by measuring F(2)-isoprostanes and prostaglandin F(2alpha), respectively, during transplantation and post-surgery. Additionally, due to earlier observations, two dissimilar anaesthetic agents (thiopentone and propofol) were compared to determine their antioxidative capacity rather than their anaesthetic properties. Blood samples were collected before, post-intubation, immediately, 30, 60,120, 240 min, and 12 and 24 h after reperfusion. Oxidative stress and inflammatory response were detected by measuring 8-iso-PGF(2alpha) (a major F(2)-isoprostane and a biomarker of oxidative stress) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha) and a biomarker of COX-mediated inflammatory response), respectively. Reperfusion of the transplanted graft significantly increased plasma levels of 8-iso-PGF(2alpha). PGF(2alpha) metabolite levels, although elevated, did not reach statistical significance. In addition, significantly lower levels of 8-iso-PGF(2a) were observed in the propofol group compared to the thiopentone group. Together, these findings underline an augmented oxidative stress activity following an inflammatory response after human renal transplantation. Furthermore, propofol a well-known anaesthetic, counteracted oxidative stress by lowering the formation of a major F(2)-isoprostane. 相似文献