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991.
The equilibrium unfolding of ElysL, a homodimeric legume lectin, was studied using different denaturing agents such as guanidinium chloride (GdnHCl), temperature and pH. Simultaneously, changes in the secondary as well as tertiary structure of lectin were followed by CD spectroscopy examination in both far and near-UV region, respectively. The hydrophobic cluster binding dye, 1-anilino-8-naphthalene sulfonate (ANS), was used to further explore intermediates and to follow the unfolding pathway of lectin. The adenine binding ability of lectin was examined and monitored via absorption spectra and the intrinsic tryptophan fluorescence. Our findings indicate that the ElysL unfolding process occurs via a three state pathway with an intermediate state. We also showed that ElysL binds adenine in a manner that involves a hydrophobic binding pocket that is independent of the carbohydrate binding sites. 相似文献
992.
Carraway RE Hassan S Cochrane DE 《Prostaglandins, leukotrienes, and essential fatty acids》2006,74(2):93-107
Neurotensin (NT) elevates leukotriene levels in animals and stimulates 5-HETE formation in prostate cancer PC3 cells. PC3 cell growth is stimulated by NT and inhibited by lipoxygenase (LOX) blockers. This led us to test LOX blockers (NDGA, MK886, ETYA, Rev5901, AA861 and others) for effects on NT binding and signaling. LOX blockers dramatically enhanced 125I-neurotensin binding to NT receptor NTR1 in PC3 cells, whereas they inhibited NT-induced inositol phosphate formation. These effects were indirect (binding to isolated membranes was unaffected), receptor-specific (binding to beta2-adrenergic, V1a-vasopressin, EGF and bombesin receptor was unaffected) and pathway-specific (cyclooxygenase inhibitors were inactive). NT receptor affinity was increased but receptor number and % internalization were unchanged. Also supporting the involvement of arachidonic acid metabolism in NTR1 regulation was the finding that inhibitors of PLA2 and DAG lipase enhanced NT binding. These findings suggest that NTR1 is regulated by specific feedback mechanism(s) involving lipid peroxidation and/or LOX-dependent processes. 相似文献
993.
Hassan SY Khattab SN Bekhit AA Amer A 《Bioorganic & medicinal chemistry letters》2006,16(6):1753-1756
A new series of 3-benzyl-2-substituted quinoxalines have been synthesized by means of microwave enhancement of nucleophilic substitution reaction involving the corresponding 2-chloroquinoxaline analogs and substituted amines or hydrazine. The synthesized compounds were evaluated for their monoamine oxidase A and B inhibitory activity by determination of their IC(50). All the newly synthesized compounds showed more selective inhibitory activity toward MAO-A than MAO-B. In addition, the acute toxicity of the synthesized compounds was determined. This work may be a fruitful matrix of the synthesis of a new series of novel MAO-A inhibitors with good safety margins. 相似文献
994.
Casañola-Martín GM Khan MT Marrero-Ponce Y Ather A Sultankhodzhaev MN Torrens F 《Bioorganic & medicinal chemistry letters》2006,16(2):324-330
In the present report, the use of the atom-based linear indices for finding functions that discriminate between the tyrosinase inhibitor compounds and inactive ones is presented. In this sense, discriminant models were applied and globally good classifications of 93.51% and 92.46% were observed for non-stochastic and stochastic linear indices best models, respectively, in the training set. The external prediction sets had accuracies of 91.67% and 89.44%. In addition, these fitted models were used in the screening of new cycloartane compounds isolated from herbal plants. A good behavior is shown between the theoretical and experimental results. These results provide a tool that can be used in the identification of new tyrosinase inhibitor compounds. 相似文献
995.
996.
Irfana Salam Showket Hussain Mohammad Muzaffar Mir Nazir Ahmad Dar Safiya Abdullah Mushtaq Ahmad Siddiqi Riyaz Ahmad Lone Showkat Ahmad Zargar Shashi Sharma Suresh Hedau Seemi Farhat Basir Alok Chandra Bharti Bhudev C. Das 《Molecular and cellular biochemistry》2009,332(1-2):51-58
Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancer in Jammu and Kashmir region of India and has multi-factorial etiology involving dietary habits, genetic factors, and gene environmental interactions. Inactivation of the p16 gene expression by aberrant promoter methylation plays an important role in the progression of esophageal carcinoma. In the present investigation, we have studied the role of p16 promoter methylation in 69 histopathologically confirmed ESCC tissues and compared it with corresponding normal adjacent tissues for DNA methylation in the CpG island in the p16 promoter region by methylation-specific polymerase chain reaction (MSP) and p16 protein expression by immunoblotting. The results showed loss of p16 expression in 67% (46/69) of tumor tissues compared to only 3% in control tissues (2/69). Promoter methylation was observed in 52% (36/69) of tumor tissues and it gradually increased with the increasing severity of histological grades of the cancer (P = 0.0001). Loss of p16 expression with promoter methylation was observed in 26 of 36 cases (72%). Analysis of patients dietary habits revealed a strong association between promoter methylation and high consumption of hot salted tea (P < 0.05) which is a most favourite drink commonly consumed by Kashmiri people. 相似文献
997.
The world-wide debate on land degradation in arid lands, usually linked to local land use practices, does not reflect methodological
advancements in terms of assessments and monitoring that integrate local communities’ knowledge with ecological methods. In
this paper, we evaluated the efficacy of three different methods related to herder assessments and monitoring of land degradation;
herder knowledge and ecological methods of assessing impacts of livestock grazing along gradients of land use from settlement
and joint monitoring of selected marked transects to understand long-term vegetation changes in southwestern Marsabit northern
Kenya. The performance of each method was carefully evaluated and interpreted in terms of the indicators used by herders and
ecologists. Herder interpretations were then related to ecologists’ empirical analysis of land degradation. The Rendille nomads
have a complex understanding of land degradation which combines environmental and livestock productivity indicators, compared
to conventional scientific approaches that use plant-based indicators alone. According to the herders, the grazing preference
of various livestock species (e.g., grazers versus browsers) influences perceptions of land degradation, suggesting degradation
is a relative term. The herders distinguished short-term changes in vegetation cover from long-term changes associated with
over-exploitation. They attributed current environmental degradation around pastoral camps, which shift land use between the
alternating wet and dry seasons, to year-round grazing. We deduced from long-term observation that herders interpret vegetation
changes in terms of rainfall variability, utilitarian values and intensification of land use. Long-term empirical data (23 years)
from repeated sampling corroborated herder interpretations. Land degradation was mostly expressed in terms of declines in
woody plant species, while spatial and temporal dynamics of herbaceous species reflected the effects of seasonality. The efficacy
of the three methods were inferred using explanatory strengths of ecological theory; insightfulness of the methods for describing
land degradation and the likelihood of using the methods for promoting local community participation in the implementation
of the UN Convention on Combating Desertification (CCD) and the Convention on Biological Diversity (CBD). 相似文献
998.
Targeted gene silencing by RNA interference allows the study of gene function in plants and animals. In cell culture and small animal models, genetic screens can be performed—even tissue-specifically in Drosophila—with genome-wide RNAi libraries. However, a major problem with the use of RNAi approaches is the unavoidable false-positive error caused by off-target effects. Until now, this is minimized by computational RNAi design, comparing RNAi to the mutant phenotype if known, and rescue with a presumed ortholog. The ultimate proof of specificity would be to restore expression of the same gene product in vivo. Here, we present a simple and efficient method to rescue the RNAi-mediated knockdown of two independent genes in Drosophila. By exploiting the degenerate genetic code, we generated Drosophila
RNAi Escape Strategy Construct (RESC) rescue proteins containing frequent silent mismatches in the complete RNAi target sequence. RESC products were no longer efficiently silenced by RNAi in cell culture and in vivo. As a proof of principle, we rescue the RNAi-induced loss of function phenotype of the eye color gene white and tracheal defects caused by the knockdown of the heparan sulfate proteoglycan syndecan. Our data suggest that RESC is widely applicable to rescue and validate ubiquitous or tissue-specific RNAi and to perform protein structure–function analysis. 相似文献
999.
Neda Karimi Zuhair Muhammad Hassan Morteza Behnam Rasuli Behrouz Ilkhanizadeh Shaker Salarilak Shahram Shahabi 《Journal of thermal biology》2009,34(6):286-289
The aim of the present study was to evaluate the role of endogenous opioids in local sublethal hyperthermia-induced protection against burn injury.Second-degree burn wounds were induced on the back of Balb/c mice. Progression of burn injury and expression of heat shock protein (HSP)-70 were evaluated after 24 h.Both inhibition of HSP synthesis and blocking opioid receptors before applying local sublethal hyperthermia decreased the protective effects of sublethal hyperthermia against the progression of burn injury. Blocking opioid receptors attenuated induction of HSP-70 by sublethal hyperthermia. 相似文献
1000.
Pyrazinamide (PZA) - an important drug in the anti-tuberculosis therapy, activated by an enzyme Pyrazinamidase (PZase). The basis of PZA
resistance in Mycobacterium tuberculosis was owing to mutation in pncA gene coding for PZase. Homology modeling of PZase was performed
using software Discovery Studio (DS) 2.0 based on the crystal structure of the PZase from Pyrococcus horikoshii (PDB code 1im5), in this study.
The model comprises of one sheet with six parallel strands and seven helices with the amino acids Asp8, Asp49, Trp68, Lys96, Ala134, Thr135
and Cys138 at the active site. Five mutants were generated with Gly at position 8, Thr at position 96, Arg at position 104, Tyr and Ser at position
138. The Wild-type (WT) and five mutant models were docked with PZA. The results indicate that the mutants Lys96Thr, Ser104Arg Asp8Gly
and Cys138Tyr may contribute to higher level drug resistance than Cys138Ser. These models provide the first in-silico evidence for the binding
interaction of PZA with PZase and form the basis for rationalization of PZA resistance in naturally occurring pncA mutant strains of M.
tuberculosis. 相似文献