全文获取类型
收费全文 | 440篇 |
免费 | 16篇 |
国内免费 | 1篇 |
出版年
2023年 | 3篇 |
2022年 | 11篇 |
2021年 | 26篇 |
2020年 | 7篇 |
2019年 | 6篇 |
2018年 | 15篇 |
2017年 | 8篇 |
2016年 | 19篇 |
2015年 | 15篇 |
2014年 | 16篇 |
2013年 | 61篇 |
2012年 | 37篇 |
2011年 | 26篇 |
2010年 | 19篇 |
2009年 | 18篇 |
2008年 | 16篇 |
2007年 | 14篇 |
2006年 | 15篇 |
2005年 | 18篇 |
2004年 | 16篇 |
2003年 | 7篇 |
2002年 | 14篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 6篇 |
1971年 | 5篇 |
1970年 | 1篇 |
排序方式: 共有457条查询结果,搜索用时 15 毫秒
91.
Sandeep Rana Yogesh A. Sonawane Margaret A. Taylor Smitha Kizhake Muhammad Zahid Amarnath Natarajan 《Bioorganic & medicinal chemistry letters》2018,28(23-24):3736-3740
We synthesized a library of aminopyrazole analogs to systematically explore the hydrophobic pocket adjacent to the hinge region and the solvent exposed region of cyclin dependent kinases. Structure-activity relationship studies identified an optimal substitution for the hydrophobic pocket and analog 24 as a potent and selective CDK2/5 inhibitor. 相似文献
92.
High mobility group A1 (HMGA1), a non-histone chromosomal protein, is highly expressed in a wide range of human cancers including cervical, breast, and prostate cancers. Therefore, hmga1 gene is considered as an attractive potential target for anticancer drugs. We have chosen 27 bp DNA sequence from a regulatory region of hmga1 promoter and studied its interaction with adriamycin (ADM) and in vitro expression of HMGA1 in the presence of ADM in HeLa cell line. A variety of biophysical techniques were employed to understand the characteristics of [DNA–ADM] complex. Spectrophotometric titration data, DNA denaturation profiles, and quenching of fluorescence of ADM in the presence of DNA demonstrated a strong complexation between DNA and ADM with a high binding affinity (Ka) of 1.3 × 106 M?1 and a stoichiometry of 1:3 (drug:nucleotide). The energetics of binding obtained from isothermal titration calorimetry and differential scanning calorimetry suggest the binding to be exothermic and enthalpy (?H, ?6.7 ± 2.4 kcal M?1) and entropy (TΔS, 18.5 ± 6.4 kcal M?1) driven (20°C), which is typical of intercalative mode of binding. Further, results on decreased expression (by ~70%) of HMGA1 both at mRNA and protein levels in association with the observed cell death (by ~75%) in HeLa cell line, clearly confirm that ADM does target hmga1; however, the effect of ADM on genes other than hmga1 either directly or via hmga1-mediated pathways cannot be ruled out in the observed cytotoxicity. Therefore, hmga1 in general and particularly the regulatory region is a promising target for therapeutic strategy in combating cancer. 相似文献
93.
The metabolism of exogenously added d-myo-[1-3H]inositol 1,4,5-trisphosphate (IP3) has been examined in microsomal membrane and soluble fractions of carrot (Daucus carota L.) cells grown in suspension culture. When [3H]IP3 was added to a microsomal membrane fraction, [3H]IP2 was the primary metabolite consisting of approximately 83% of the total recovered [3H] by paper electrophoresis. [3H]IP was only 6% of the [3H] recovered, and 10% of the [3H]IP3 was not further metabolized. In contrast, when [3H]IP3 was added to the soluble fraction, approximately equal amounts of [3H]IP2 and [3H]IP were recovered. Ca2+ (100 micromolar) tended to enhance IP3 dephosphorylation but inhibited the IP2 dephosphorylation in the soluble fraction by about 20%. MoO42− (1 millimolar) inhibited the dephosphorylation of IP3 by the microsomal fraction and the dephosphorylation of IP2 by the soluble fraction. MoO42−, however, did not inhibit the dephosphorylation of IP3 by the soluble fraction. Li+ (10 and 50 millimolar) had no effect on IP3 metabolism in either the soluble or membrane fraction; however, Li+ (50 millimolar) inhibited IP2 dephosphorylation in the soluble fraction about 25%. 相似文献
94.
Memon MA Archbald LF Olcott BM Memon HS Oz HH Chandler JE Ingraham RH 《Theriogenology》1986,25(5):653-658
Results of two experiments are described. In the first experiment, forty-one mixed-breed goats (does) with unknown gestation lengths were given 10 mg prostaglandin F(2alpha) (PGF(2alpha)) (2 doses of 5 mg each, 24 h apart) i.m. Blood samples were obtained before each treatment with PGF(2alpha) by jugular venipuncture, and plasma progesterone (P(4)) concentrations were determined by a nonextraction solid-phase radioimmunoassay. P(4) concentrations (ng/ml) were significantly decreased (15.47 vs 1.55, P<0.005) 24 h after the first injection of PGF(2alpha). A total of 63 fetuses was collected within 46.5 h following the first injection. Mean (+/- SE) crownrump lengths and body weights of 62 fetuses were 21.46 +/- 0.29 centimeters (cm) and 575.00 +/- 20.60 g, respectively. Based on these findings, the mean gestation length of these does was estimated to be 86.96 +/- 0.74 d. Thirty-one does retained their placenta for 12 to 72 h and were treated with a single injection of 5 mg PGF(2alpha) and 800 mg oxytetracycline i.m. Placental expulsion in all does occurred within 24 h posttreatment. The results of this study suggest that two doses of 5 mg PGF(2alpha) intramuscularly (i.m.) 24 h apart is an effective abortifacient at about 3 mo of pregnancy in does. In the second experiment, 38 does from the first experiment were divided in two groups of 19 each on Day 13 postabortion. Group A (treated) was given 50 ug GnRH i.m. while Group B (control) received 1 ml 0.9% saline i.m. Blood samples were obtained prior to treatment and on Day 23 postabortion and assayed for P(4) concentrations. There was no significant difference (P>0.10) in P(4) concentrations of samples obtained pre- and post-GnRH treatment. However, 14 of 19 and 12 of 19 in Groups A and B, respectively, exhibited estrus within 52 days following abortion. Twenty-six does were bred naturally and 17 became pregnant. 相似文献
95.
Zahid Mozaffar Kazuhiro Nakanishi Ryuichi Matsuno 《Applied microbiology and biotechnology》1986,25(3):229-231
Summary The specific activity-dependent stability of the immobilized -galactosidase-2 (-d-galactoside galactohydrolase, EC 3.2.1.23) from Bacillus circulans during the continuous production of galactooligosaccharides from lactose was studied. This was done by measuring the elution pattern of saccharides from the various immobilized Merckogel (controlled pore silica gel) columns and the amount of saccharides remaining in the gel. It was suggested that oligosaccharides produced were trapped inside the three dimensional enzyme aggregate with the immobilized enzyme having a specific activity of 240 units/g of wet gel, causing gradual inactivation, while the immobilized enzyme with 15 units/g of wet gel was stable since the oligosaccharides were not accumulated.Free -galactosidase-2 was stable during continuous reaction in a membrane reactor. 相似文献
96.
Microdistribution of manganese in the leaf tissues of different plant species as revealed by X-ray microanalyzer 总被引:1,自引:0,他引:1
Abdul Razaque Memon Mitsuo Chino Kouichi Hara Michihiko Yatazawa 《Physiologia plantarum》1981,53(3):225-232
Microdistribution patterns of Mn in the leaf tissues of 9 plant species, Quercus mongolica Fisch. var. grosseserrata Rehd. et Wils., Lindera erythrocarpa Makino, Rhus trichocarpa Miq., Ilex crenata Thunb. var paludosa (Nakai) Hara, Acer sieboldianum Miq., Acanthopanax sciadophylloides Franch. et Savat., Clethra barbinervis Sieb. et Zucc., Pieris japonica (Thunb.) D. Don and Rhododendron semibarbatum Maxim. were studied by means of a wavelength dispersive type X-ray microanalyzer in conjunction with cryostage. The results showed that Mn, in general, was highly concentrated in the epidermal, palisade and spongy parenchyma cells of the leaf tissues of the investigated plants with optimal Mn supply. 相似文献
97.
The proteinases present in dark-germinated flax seeds (Linum usitatissimum) were studied as a function of germination at 25°C. A majority of activity was present in basic proteinases with an acidic pH optimum and a temperature optimum of 45°C in the digestion of hemoglobin. Electrophoresis in a sodium dodecyl sulfate-polyacrylamide mixture which had been polymerized with gelatin was used to separate proteins in extracts of seedlings. Subsequent activation of proteinases with Triton X-100 and resultant digestion of gelatin proved to be very reproducible and afforded detection and good quantification of various proteinase zones. An ethylenediaminetetraacetate-sensitive proteinase zone, P4 (about 60,000 daltons), appeared at day 3 after imbibition and attained maximum activity at day 4. This correlates with a rapid loss in vivo of the glyoxysomal enzyme, isocitrate lyase (EC 4.1.3.1). Ethylenediaminetetraacetate also slowed the loss of isocitrate lyase activity in extracts of 4-day seedlings in a dose-dependent manner. The addition of leupeptin, α-tolylsulfonyl fluoride, Pepstatin A, p-chloromercuribenzoate, or 1,10-phenanthroline prior to, during, or after exchange of Triton X-100 for sodium dodecyl sulfate had almost no inhibitory effect upon proteinases in 4-day seedlings. 相似文献
98.
Zahid Mozaffar Kazuhiro Nakanishi Ryuichi Matsuno 《Applied microbiology and biotechnology》1987,25(5):426-429
Summary The oligosaccharide-producing activity of -galactosidase-1, one of the isomers of -galactosidase (-d-galactoside galactohydrolase, EC 3.2.1.23) from Bacillus circulans was changed after immobilization onto porous silica gel (Merckogel) by crosslinkage with glutaraldehyde. The reason for this modification was studied by treating the free enzyme with glutaraldehyde. Glutaraldehyde of 0.025% to 3% modified 40% to 90% of the free amino groups with or without intermolecular crosslinking. The maximum yield of oligosaccharides increased from 12% to 40% depending upon degree of modification, while native enzyme gave only 6% trisaccharides during hydrolysis of 127 mM lactose. The K
m
value for the enzyme treated with glutaraldehyde was also increased. 相似文献
99.
Reserpine was administered to an 8-yr-old Thoroughbred stallion at a dosage of 5 mg subcutaneously (s.c.) every 2 wk for a 2-mo period to control unmanageable behavior. Reserpine produced a satisfactory calming effect that lasted for about 2 wk. After the last injection, the stallion developed penile paralysis and was unable to retract his penis, resulting in paraphimosis and attendant penile edema. The prolapsed penis was reduced and kept within the prepuce by placing a purse string suture in the preputial orifice. Phenylbutazone was given orally (1 gm) and the stallion was exercised for 20 to 30 min twice daily. This treatment was continued for 20 d with little improvement. The purse string retention suture cut through the skin 5 d after the stallion was discharged from the clinic. The penis was then supported against the abdominal wall and the stallion was exercised by hand for 30 min each day. The stallion was not used for breeding within 34 mo after the last injection of reserpine. A breeding soundness examination was performed approximately 3 yr after the initial injury. At this time the stallion's penis was noted to extend 5 to 8 cm from the prepuce when in a detumescent state. Although the stallion protruded his penis when exposed to a mare in estrus, a full rigid erection was never attained. Examination of the penis revealed partial engorgement of the corpus cavernosum penis and a 2.5-cm-wide dorsal semi-circumferential depression of the penile shaft approximately 10 to 12 cm proximal to the glans penis. The penile shaft and glans penis distal to this depression were cooler than the proximal portion of the penis. Semen collection was attempted, aided by manual insertion of the penis into the artificial vagina. When serving the artificial vagina, no "belling" of the glans penis was observed, although ejaculation occurred. Semen evaluation indicated normal spermatozoal motility and morphology parameters. The stallion was able to breed several mares with manual assistance to guide the penis into the vagina and one mare was diagnosed pregnant. 相似文献
100.