全文获取类型
收费全文 | 9111篇 |
免费 | 757篇 |
国内免费 | 367篇 |
出版年
2024年 | 28篇 |
2023年 | 205篇 |
2022年 | 294篇 |
2021年 | 525篇 |
2020年 | 491篇 |
2019年 | 543篇 |
2018年 | 477篇 |
2017年 | 338篇 |
2016年 | 345篇 |
2015年 | 389篇 |
2014年 | 738篇 |
2013年 | 770篇 |
2012年 | 466篇 |
2011年 | 624篇 |
2010年 | 476篇 |
2009年 | 416篇 |
2008年 | 394篇 |
2007年 | 436篇 |
2006年 | 362篇 |
2005年 | 331篇 |
2004年 | 287篇 |
2003年 | 247篇 |
2002年 | 263篇 |
2001年 | 149篇 |
2000年 | 86篇 |
1999年 | 85篇 |
1998年 | 72篇 |
1997年 | 71篇 |
1996年 | 44篇 |
1995年 | 41篇 |
1994年 | 39篇 |
1993年 | 30篇 |
1992年 | 27篇 |
1991年 | 17篇 |
1990年 | 10篇 |
1989年 | 11篇 |
1988年 | 14篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 9篇 |
1984年 | 15篇 |
1983年 | 17篇 |
1982年 | 9篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1975年 | 2篇 |
1973年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 125 毫秒
41.
J. Garforth J. H. McKie R. Jaouhari T. J. Benson A. H. Fairlamb K. T. Douglas 《Amino acids》1994,6(3):295-299
Summary The rational design of ligands for the substrate-binding site of a homology-modelled trypanothione reductase (TR) was performed. Peptides were designed to be selective for TR over human glutathione reductase (GR). The design process capitalized on the proposed differences between the activesites of TR and human GR, subsequently confirmed by the TR crystal structure. Enzyme kinetics confirmed that forT. cruzi TR benzoyl-Leu-Arg-Arg-ß-naphthylamide was an inhibitor (Ki 13.8µM) linearly competitive with the native substrate, trypanothione disulphide, and did not inhibit glutathione reductase. 相似文献
42.
43.
Gary C. du Moulin Zorina Pitkin Yuan-Jin Shen Evelyn Conti Jean Ko Stewart Carla Charles Dylan Hamilton 《Cytotechnology》1994,15(1-3):365-372
Somatic cell and gene therapy involve the application of biological technologies to an individual patient through the use of living cells which provide a therapeutic benefit (Aliski, 1991). Various forms of cellular and gene therapies are being developed and evaluated in an increasing number of clinical trials for congential and acquired disorders. The potential and progress of these therapeutic applications have resulted in an increasing effort by the Food and Drug Administration (FDA) to develop the regulatory framework under which these therapeutic approaches would insure safety and efficacy, the primary mandate of the FDA.Over five years ago Cellcor began to define the parameters, specifications, and conditions relevant to a Quality Assurance/Quality Control (QA/QC) program that has evolved to insure safety and maximize the efficacy of applications of the company'sex vivo technology, autolymphocyte therapy. Autolymphocyte therapy is an outpatient form of somatic cell immunotherapy based upon the infusion of T cells that have been activatedex vivo using a combination of previously generated autologous cytokines and an anti-CD3 monoclonal antibody.We have been able to demonstrate the feasibility for the safe, controlled, and consistent preparation and delivery of a cellular therapy by application of relevant GMP regulations. This presentation reviews aspects of this program and chronicles our experience which at present amounts to over 4400 infusions for over 700 patients. This program provides a high degree of assurance that a cellular therapy program can be carried out in a multisite mode involving hundreds of patients through the strict adherence to cGMP as set forth in existing regulations. It would be prudent that developers of cellular andex vivo gene therapies establish a similar cell processing and QA/QC infrastructure at an early developmental stage to optimize safety and reproducibility and facilitate regulatory review. 相似文献
44.
45.
本文应用系统分析方法,建立了一种一级吸收药物的生物利用度的简便估计的两点法。这种方法,只需测量血管内和血管外给药后的两个相同时点的血药浓度值。不论该药的处置系统是多少室,均能得到较好的结果。这种方法不仅比目前常用的点一点法和点一面法简单,而且结果更精确。 相似文献
46.
Bosslet K. Czech J. Seemann G. Monneret C. Hoffmann D. 《Cell biochemistry and biophysics》1994,24(1-3):51-63
A two component system, consisting of a fusion protein and an appropriate prodrug, suited to perform selective tumor therapy
in vivo, is presented. The fusion protein, owing to its humanized carcinoembryonic antigen (CEA)-specific variable region,
specifically binds to CEA-expressing tumors and has an enzymatic activity comparable to human β-glucuronidase. The prodrug
is a nontoxic glucuronide-spacer-derivative of doxorubicin decomposing to doxorubicin by enzymatic deglucuronidation.
In vivo studies in nude mice bearing human CEA-expressing tumor xenografts revealed that 7 d after injection of 20 mg/kg fusion
protein, a high specificity ratio (>100:1) was obtained between tumor and plasma. Injection of 250 mg/kg of prodrug at d 7
resulted in tumor therapeutic effects superior to conventional chemotherapy without any detectable toxicity. These superior
therapeutic effects that were observed using established human tumor xenografts can be explained by the approx 10-fold higher
drug concentrations found in tumors of mice treated with fusion protein and prodrug than in those treated with the maximal
tolerable dose of drug alone. 相似文献
47.
48.
《Saudi Journal of Biological Sciences》2023,30(8):103730
Mycobacterium tuberculosis (MTB) is becoming more and more resistant to drugs and it is a common problem, making current antimicrobials ineffective and highlighting the need for new TB drugs. One of the promising targets for treating MTB is MurB enzymes. This study aimed to identify potential inhibitors of MurB enzymes in M. tuberculosis, as drug resistance among MTB is a significant problem. Attempts are being made to conduct a virtual screening of 30,417 compounds, and thirty-two compounds were chosen for further analysis based on their binding conformations. The selected compounds were assessed for their drug-likeness, pharmacokinetics, and physiochemical characteristics, and seven compounds with binding energy lower than flavin (FAD) were identified. Further, molecular dynamics simulation analysis of these seven compounds found that four of them, namely DB12983, DB15688, ZINC084726167, and ZINC254071113 formed stable complexes with the MurB binding site, exhibiting promising inhibitory activity. These compounds have not been mentioned in any other study, indicating their novelty. The study suggests that these four compounds could be promising candidates for treating MTB, but their effectiveness needs to be validated through in vitro and in vivo experiments. Overall, the findings of this study provide new insight into potential drug targets and candidates for combating drug-resistant MTB. 相似文献
49.
Wen Gao Ying Xu Jianxiang Liu Xiaolei Wang Xinhong Dong Guigen Teng Binbin Liu Jinpei Dong Chaoyi Ge Hui Ye Xuezhi Zhang Hong Cheng 《Helicobacter》2023,28(2):e12947
Background
The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin.Objective
To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies.Design
Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by 13C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing.Results
A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline.Conclusions
For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin. 相似文献50.
Hrushikesh S. Chaudhari Omkar S. Palkar KM Abha Mishra Kalyan K. Sethi 《Journal of biochemical and molecular toxicology》2023,37(9):e23417
During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B ( 1 ) and isavuconazole ( 2 ) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole ( 3 ) and deferasirox ( 4 ) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 ( 5 ) and APX001A ( 6 ), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis. 相似文献