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171.
One new eudesmane sesquiterpenoid, 11β-hydroxy-13-chloro-eudesm-5-en-12, 8-olide (1), was isolated from the roots of Inula helenium together with nine eudesmanolides (2–10) and one germacranolide (11). Their structures were elucidated on the basis of detailed spectroscopic analyses. All isolates were evaluated for their antiproliferative activities against human leukemia stem-like cell line KG1a. Compound 10 exhibited the most potent effect with the IC50 value of 3.36 ± 0.18 μM. A further investigation revealed that compound 10 could significantly induce apoptosis of KG1a cells. Additionally, compound 10 had an obvious effect on the levels of apoptosis-related proteins (Bcl-2, Bax, cytochrome c, caspase 9 and caspase 3), indicating that the antiproliferative effect of compound 10 on KG1a cells might be mediated through a mitochondria-dependent apoptotic pathway. 相似文献
172.
Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008–2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores. 相似文献
173.
In this work, we study the effect of different variables affecting elution profile distortion on the enantiomeric resolution eventually achievable when working with on‐line coupled liquid chromatography to gas chromatography (LC‐GC). Specifically, the proposed configuration combines achiral reversed‐phase liquid chromatography (RPLC) and chiral gas chromatography (enantio‐GC), with heptakis‐(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin as enantioselective stationary phase to analyse target fractions transferred (from LC to GC) via the through oven transfer adsorption desorption (TOTAD) interface. The high degree of orthogonality resulting from the combination of two chromatographic columns having very different separation mechanisms (and also requiring mobile phases in distinct physical states), as well as integration of the sample preparation step in the first dimension of the system, significantly contributed to exploit the performance of the proposed two‐dimensional approach. Occasional adverse effects, which may result in severe peak distortions during LC‐GC analysis and could be explained by flow instabilities due to viscous fingering, are circumvented by using the outstanding capacity of the TOTAD interface for achieving effective elimination of the eluent arriving from the LC preseparation. 相似文献
174.
Apoptosis is a form of programmed and controlled cell death that accounts for the majority of cellular death in bioprocesses. Cell death affects culture longevity and product quality; it is instigated by several stresses experienced by the cells within a bioreactor. Understanding the factors that cause apoptosis as well as developing strategies that can protect cells is crucial for robust bioprocess development. This review aims to a) address apoptosis from a bioprocess perspective; b) describe the significant apoptotic mechanisms linking them to the most relevant stresses encountered in bioreactors; c) discuss the design of operating conditions in order to avoid cell death; d) focus on industrially relevant cell lines; and e) present anti-apoptosis strategies including cell engineering and model-based optimization of bioprocesses. In addition, the importance of apoptosis in quality-by-design bioprocess development from clone screening to production scale are highlighted. 相似文献
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176.
Maninder Kaur Yogesh Vikal Harleen Kaur Lalit Pal Kirandeep Kaur Jasbir Singh Chawla 《Journal of Phytopathology》2019,167(10):591-600
Southern leaf blight (SLB) caused by the fungus Cochliobolus heterostrophus (Drechs.) Drechs. is a major foliar disease of maize worldwide. Our objectives were to identify quantitative trait loci (QTL) for resistance to SLB and flowering traits in recombinant inbred line (RIL) population derived from the cross of inbred lines LM5 (resistant) and CM140 (susceptible). A set of 207 RILs were phenotyped for resistance to SLB at three time intervals for two consecutive years. Four putative QTL for SLB resistance were detected on chromosomes 3, 8 and 9 that accounted for 54% of the total phenotypic variation. Days to silking and anthesis–silking interval (ASI) QTL were located on chromosomes 6, 7 and 9. A comparison of the obtained results with the published SLB resistance QTL studies suggested that the detected bins 9.03/02 and 8.03/8.02 are the hot spots for SLB resistance whereas novel QTL were identified in bins 3.08 and 8.01/8.04. The linked markers are being utilized for marker‐assisted mobilization of QTL conferring resistance to SLB in elite maize backgrounds. Fine mapping of identified QTL will facilitate identification of candidate genes underlying SLB resistance. 相似文献
177.
Ke Zhang Dan Baeckstrm Hans Brevinge Gunnar C. Hansson 《Journal of cellular biochemistry》1996,60(4):538-549
A secreted MUC1 mucin from the spent medium of the colon carcinoma cell line COLO 205 carrying sialyl-Lewis a and x epitopes (H-CanAg) was purified by trichloroacetic acid precipitation and Superose 6 gel filtration. The purified H-CanAg inhibited adhesion of the leukocyte cell line HL-60 to E-selectin transfected COS-1 cells or interleukin-1β (IL-1β)-activated human umbilical vein endothelial cells. Sera from two patients with advanced colon carcinoma containing high concentrations of sialyl-Lewis a and x activity inhibited HL-60 cell adhesion to E-selectin-expressing COS-1 cells and IL-1β-activated endothelial cells. After affinity column absorption of the sialyl-Lewis a activity, the sera also lost most of their sialyl-Lewis x activity and at the same time their adhesion inhibitory effect. A large part of the sialyl-Lewis a/x activity in the two patients was found in fractions containing mucins having a MUC1 apoprotein, as shown by its size, and reactivity with the two anti-MUC1 apoprotein monoclonal antibodies, Ma552 and HMFG-2. The cell-adhesion inhibitory effect of the purified sialyl-Lewis a-carrying MUC1 mucin fraction from the sera of the two patients was stronger than that of smaller sized sialyl-Lewis a-carrying mucin-type glycoproteins also found in the patient sera. The MUC1 mucin fraction secreted by the COLO 205 cells and from the two sera were all shown to lack their C-terminal portion, in contrast to the MUC1 mucin from cells. It is hypothesized that sialyl-Lewis a- and/or x-containing mucins, especially MUC1, secreted by tumors can interact with E-selectin on endothelial cells and thus inhibit leukocyte adhesion. © 1996 Wiley-Liss, Inc. 相似文献
178.
Over the last 20 years, studies of Caenorhabditis elegans natural diversity have demonstrated the power of quantitative genetic approaches to reveal the evolutionary, ecological, and genetic factors that shape traits. These studies complement the use of the laboratory-adapted strain N2 and enable additional discoveries not possible using only one genetic background. In this chapter, we describe how to perform quantitative genetic studies in Caenorhabditis, with an emphasis on C. elegans. These approaches use correlations between genotype and phenotype across populations of genetically diverse individuals to discover the genetic causes of phenotypic variation. We present methods that use linkage, near-isogenic lines, association, and bulk-segregant mapping, and we describe the advantages and disadvantages of each approach. The power of C. elegans quantitative genetic mapping is best shown in the ability to connect phenotypic differences to specific genes and variants. We will present methods to narrow genomic regions to candidate genes and then tests to identify the gene or variant involved in a quantitative trait. The same features that make C. elegans a preeminent experimental model animal contribute to its exceptional value as a tool to understand natural phenotypic variation. 相似文献
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180.