全文获取类型
收费全文 | 28990篇 |
免费 | 2269篇 |
国内免费 | 54篇 |
专业分类
耳鼻咽喉 | 197篇 |
儿科学 | 928篇 |
妇产科学 | 714篇 |
基础医学 | 4017篇 |
口腔科学 | 337篇 |
临床医学 | 4154篇 |
内科学 | 5124篇 |
皮肤病学 | 632篇 |
神经病学 | 2942篇 |
特种医学 | 587篇 |
外科学 | 3119篇 |
综合类 | 267篇 |
一般理论 | 65篇 |
预防医学 | 3719篇 |
眼科学 | 421篇 |
药学 | 1814篇 |
中国医学 | 21篇 |
肿瘤学 | 2255篇 |
出版年
2023年 | 275篇 |
2022年 | 367篇 |
2021年 | 824篇 |
2020年 | 599篇 |
2019年 | 793篇 |
2018年 | 953篇 |
2017年 | 697篇 |
2016年 | 735篇 |
2015年 | 752篇 |
2014年 | 1091篇 |
2013年 | 1595篇 |
2012年 | 2339篇 |
2011年 | 2445篇 |
2010年 | 1298篇 |
2009年 | 1130篇 |
2008年 | 1921篇 |
2007年 | 2024篇 |
2006年 | 1857篇 |
2005年 | 1737篇 |
2004年 | 1572篇 |
2003年 | 1378篇 |
2002年 | 1353篇 |
2001年 | 240篇 |
2000年 | 257篇 |
1999年 | 234篇 |
1998年 | 266篇 |
1997年 | 216篇 |
1996年 | 180篇 |
1995年 | 135篇 |
1994年 | 143篇 |
1993年 | 129篇 |
1992年 | 147篇 |
1991年 | 141篇 |
1990年 | 117篇 |
1989年 | 120篇 |
1988年 | 90篇 |
1987年 | 88篇 |
1986年 | 97篇 |
1985年 | 93篇 |
1984年 | 82篇 |
1983年 | 65篇 |
1982年 | 65篇 |
1981年 | 48篇 |
1979年 | 57篇 |
1978年 | 45篇 |
1977年 | 45篇 |
1976年 | 43篇 |
1974年 | 46篇 |
1973年 | 45篇 |
1970年 | 33篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
993.
994.
Stephen Weller Julie Borland Shuguang Chen Mark Johnson Paul Savina Brian Wynne Toshihiro Wajima Amanda F. Peppercorn Stephen C. Piscitelli 《European journal of clinical pharmacology》2014,70(1):29-35
Purpose
Dolutegravir (DTG), an unboosted HIV integrase inhibitor (INI), is metabolized by UGT1A1 and to a minor extent by CYP3A. Renal elimination of unchanged DTG is very low (< 1 %). As renal impairment may affect pharmacokinetics (PK), even for drugs primarily metabolized or secreted in bile, this study investigated the effect of renal impairment on the PK of DTG.Methods
This was an open-label, single-dose study of oral DTG 50 mg administered to subjects with severe renal impairment (creatinine clearance [CLcr] <30 mL/min; not on dialysis) and to healthy controls (CLcr >90 mL/min) matched for gender, age and body mass index (8 subjects per group). Serial PK samples were collected up to 72 h post-dose for determination of DTG and DTG-glucuronide (DTG-Gluc) concentrations in plasma. DTG unbound fraction in plasma was determined at 3 and 24 h. PK parameters were determined by non-compartmental methods and compared between groups by analysis of covariance.Results
DTG was well tolerated with a low incidence of Grade 1 adverse events. DTG PK parameters showed significant overlap between groups. DTG mean exposure was lower in subjects with severe renal impairment compared to healthy, matched subjects: AUC(0-∞) and Cmax were 40 % and 23 % lower, while mean DTG-Gluc was increased. Renal impairment did not affect DTG fraction unbound in plasma.Conclusions
The modest reductions in mean PK exposures for DTG and increases for DTG-Gluc in the severe renal impairment group are not considered clinically significant. DTG does not require dose adjustment in patients with renal impairment. 相似文献995.
Julie K. Klint Géza Berecki Thomas Durek Mehdi Mobli Oliver Knapp Glenn F. King David J. Adams Paul F. Alewood Lachlan D. Rash 《Biochemical pharmacology》2014
Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-Cc1a (Cc1a), from the venom of the tarantula Citharischius crawshayi (now Pelinobius muticus). Cc1a is 67% identical to the spider toxin ω-TRTX-Hg1a, an inhibitor of CaV2.3 channels. We assembled Cc1a using a combination of Boc solid-phase peptide synthesis and native chemical ligation. Oxidative folding yielded two stable, slowly interconverting isomers. Cc1a preferentially inhibited Ba2+ currents (IBa) mediated by L-type (CaV1.2 and CaV1.3) CaV channels heterologously expressed in Xenopus oocytes, with half-maximal inhibitory concentration (IC50) values of 825 nM and 2.24 μM, respectively. In rat dorsal root ganglion neurons, Cc1a inhibited IBa mediated by high voltage-activated CaV channels but did not affect low voltage-activated T-type CaV channels. Cc1a exhibited weak activity at NaV1.5 and NaV1.7 voltage-gated sodium (NaV) channels stably expressed in mammalian HEK or CHO cells, respectively. Experiments with modified Cc1a peptides, truncated at the N-terminus (ΔG1–E5) or C-terminus (ΔW35–V39), demonstrated that the N- and C-termini are important for voltage-gated ion channel modulation. We conclude that Cc1a represents a novel pharmacological tool for probing the structure and function of L-type CaV channels. 相似文献
996.
The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110–545, Arlington, VA 22203, e-mail: ten.tsacmoc@cvSxRcnO; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: ten.retrahc@ruofddaw.Regimen Name: Paclitaxel and CarboplatinSynonym: TCOrigin of Name: TC is an acronym for the 2 medications in the regimen: paclitaxel (Taxol) and carboplatin. 相似文献
997.
Julie E. Goodman Michael K. Peterson Lisa A. Bailey Laura E. Kerper David G. Dodge 《Regulatory toxicology and pharmacology : RTP》2014
Both mechanistic and epidemiology studies indicate chrysotile asbestos has a threshold below which it does not cause mesothelioma or lung cancer. We conducted a critical review to determine whether electricians are at increased risk for these cancers and, if so, whether their exposure to chrysotile in electrical products could be responsible. We found that most, but not all, epidemiology studies indicate electricians are at increased risk for both cancers. Studies that evaluated electricians’ exposure to asbestos during normal work tasks have generally reported low concentrations in air; an experimental study showed that grinding or drilling products containing encapsulated chrysotile resulted in exposures to chrysotile fibers far below the OSHA permissible exposure limit and the cancer no observed adverse effect level. Studies of other craftsmen who often work in the vicinity of electricians, such as insulators, reported asbestos (including amphibole) exposures that were relatively high. Overall, the evidence does not indicate that exposure to chrysotile in electrical products causes mesothelioma or lung cancer in electricians. Rather, the most likely cause of lung cancer in electricians is smoking, and the most likely cause of mesothelioma is exposure to amphibole asbestos as a result of renovation/demolition work or working in the proximity of other skilled craftsmen. 相似文献
998.
Monomethylated trivalent arsenic species disrupt steroid receptor interactions with their DNA response elements at non‐cytotoxic cellular concentrations
下载免费PDF全文
![点击此处可从《Journal of applied toxicology : JAT》网站下载免费的PDF全文](/ch/ext_images/free.gif)
999.
In 2011, the Australian National Health and Medical Research Council (NHMRC) initiated an inquiry to determine whether there is a need for expanded ethical guidance in the form of a discrete guidance document for alcohol and other drug (AOD) research. An issues paper was developed to frame the inquiry. AOD researchers, Human Research Ethics Committees and others were invited to discuss whether there are distinctive ethical issues facing researchers and Human Research Ethics Committees in the AOD setting. Based on the public submissions, the NHMRC recommended that no AOD research‐specific guidance is required. The inquiry and the NHMRC decision were not widely publicized, and we feel there is a need for further discussion. In order to do so, we have analysed the public inquiry submissions and described the central themes. Few submissions in the inquiry explicitly agreed AOD research warrants a specific guidance framework. Most were concerned that the NHMRC issues paper unfairly targeted people who use drugs as complex research participants. The inquiry highlights tensions around research governance and ethics review boards dealing with illicit and stigmatised behaviours. While we agree that a specific guidance framework for AOD research is not needed and could potentially be harmful and restrictive, we are concerned that the wholesale rejection of a guidance framework has closed the door to much needed debate. There remains, we argue, a need for alternative strategies and tools to support ethical research, inform and streamline institutional ethics approval, and engage and protect participants. [Olsen A, Mooney‐Somers J. Is there a problem with the status quo? Debating the need for standalone ethical guidelines for research with people who use AODs. Drug Alcohol Rev 2014;33:637‐642] 相似文献
1000.
Lois A. Jackson Susan McWilliam Fiona Martin Julie Dingwell Margaret Dykeman Jacqueline Gahagan 《Drugs (Abingdon, England)》2014,21(3):244-253
Aims: Many people who use drugs (PWUD) have multiple health and social needs, and research suggests that this population is increasingly accessing emergency departments (EDs) and shelters for health care and housing. This qualitative study explored the practices of those working in EDs and shelters when providing services to PWUD, with a particular focus on key challenges in service provision. Methods: EDs and shelters were conceptualized as ‘micro environments’ with various components (i.e. social, physical and resource). One-on-one interviews were conducted with 57 individuals working in EDs and shelters in Atlantic Canada. Findings: The social, physical and resource environments within some EDs and shelters are key forces in shaping the challenges facing those providing services. For example, the social environments within these settings are focused on acute health care in the case of EDs, and housing in the case of shelters. These mandates do not encompass the complex needs of many PWUD. Resource issues within the wider community (e.g. limited drug treatment spaces) further contribute to the challenges. Conclusions: Structural issues, internal and external to EDs and shelters need to be addressed to reduce the challenges facing many who work in these settings when providing services to PWUD. 相似文献