全文获取类型
收费全文 | 908篇 |
免费 | 48篇 |
国内免费 | 34篇 |
专业分类
化学 | 339篇 |
力学 | 15篇 |
综合类 | 17篇 |
数学 | 35篇 |
物理学 | 86篇 |
综合类 | 498篇 |
出版年
2024年 | 4篇 |
2023年 | 15篇 |
2022年 | 103篇 |
2021年 | 87篇 |
2020年 | 24篇 |
2019年 | 27篇 |
2018年 | 20篇 |
2017年 | 22篇 |
2016年 | 18篇 |
2015年 | 22篇 |
2014年 | 36篇 |
2013年 | 31篇 |
2012年 | 30篇 |
2011年 | 41篇 |
2010年 | 32篇 |
2009年 | 39篇 |
2008年 | 30篇 |
2007年 | 34篇 |
2006年 | 46篇 |
2005年 | 35篇 |
2004年 | 55篇 |
2003年 | 38篇 |
2002年 | 32篇 |
2001年 | 24篇 |
2000年 | 27篇 |
1999年 | 14篇 |
1998年 | 9篇 |
1997年 | 12篇 |
1996年 | 14篇 |
1995年 | 11篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 6篇 |
1991年 | 7篇 |
1990年 | 3篇 |
1989年 | 9篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1984年 | 4篇 |
1977年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有990条查询结果,搜索用时 0 毫秒
41.
Tomasz Ligor Joanna Zawadzka Grzegorz Strczyski Rosa M. Gonzlez Paredes Anna Wenda-Piesik Ileana Andreea Ratiu Marek Muszytowski 《Molecules (Basel, Switzerland)》2021,26(7)
Volatile organic compounds (VOCs) exiting in urine are potential biomarkers of chronic kidney diseases. Headspace solid phase microextraction (HS-SPME) was applied for extraction VOCs over the urine samples. Volatile metabolites were separated and identified by means of two-dimensional gas chromatography and time of flight mass spectrometry (GC × GC TOF MS). Patients with glomerular diseases (n = 27) and healthy controls (n = 20) were recruited in the study. Different VOCs profiles were obtained from patients and control. Developed methodology offers the opportunity to examine the metabolic profile associated with glomerulopathy. Four compounds found in elevated amounts in the patients group, i.e., methyl hexadecanoate; 9-hexadecen-1-ol; 6,10-dimethyl-5,9-undecadien-2-one and 2-pentanone were proposed as markers of glomerular diseases. 相似文献
42.
Jacinthe Frangieh Mohamad Rima Ziad Fajloun Daniel Henrion Jean-Marc Sabatier Christian Legros Csar Mattei 《Molecules (Basel, Switzerland)》2021,26(8)
Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs. 相似文献
43.
《印度化学会志》2021,98(10):100156
Corona virus disease 2019 (COVID-19) endemic has havoc on the world; the causative virus of the pandemic is SARS CoV-2. Pharmaceutical companies and academic institutes are in continuous efforts to identify anti-viral therapy or vaccines, but the most significant challenge faced is the highly evolving genome of SARS CoV-2, which is imparting evolutionary selective benefits to the virus. To understand the viral mutations, we have retrieved nine hundred and thirty-four samples from different states of India via the GISAID database and analyzed the frequency of all types of point mutation in all structural, non-structural proteins, and accessory factors of SARS CoV-2. Spike glycol protein, nsp3, nsp6, nsp12, N and NS3 were the most evolving proteins. High frequency point mutations were Q496P (nsp2), A380V (nsp4), A994D (nsp3), L37F (nsp6), P323L & A97V (nsp12), Q57H (ns3), D614G (S), P13L (N), R203K (N), G204R (N) and S194L (N). 相似文献
44.
胡斌 《广东微量元素科学》1997,4(9):51-55
儿童缺锌是较普遍的社会现象,济南泉城微量元素生命研究所研制的复合蛋白锌系采用生物技术转化而得到的一种蛋白复合物,属生物合成的有机微量元素,经急性和长期毒性试验均未发现毒副作用,经检测不含兴奋剂,用于临床后,对纠正偏食厌食,反复呼吸道感染和智力低下等近千例儿童疾患,显示了可喜的临床效果,证明是优质有机补锌剂。 相似文献
45.
调查了内蒙古青山区8~10岁儿童碘缺乏病甲状腺肿大率,结果表明,甲状腺肿大率为19.6%,且以城乡结合部居住儿童为高,监测了其尿碘,尿碘水平100μg/L以下者为11.2%,其中50μg/L者了有发现,据此情况,今后仍要强化防治工作。 相似文献
46.
Julien Antih Marketa Houdkova Klara Urbanova Ladislav Kokoska 《Molecules (Basel, Switzerland)》2021,26(21)
While the inhalation of Thymus vulgaris L. essential oil (EO) is commonly approved for the treatment of mild respiratory infections, there is still a lack of data regarding the antimicrobial activity and chemical composition of its vapours. The antibacterial activity of the three T. vulgaris EOs against respiratory pathogens, including Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pyogenes, was assessed in both liquid and vapour phases using the broth microdilution volatilisation (BMV) method. With the aim of optimising a protocol for the characterisation of EO vapours, their chemical profiles were determined using two headspace sampling techniques coupled with GC/MS: solid-phase microextraction (HS-SPME) and syringe headspace sampling technique (HS-GTS). All EO sample vapours exhibited antibacterial activity with minimum inhibitory concentrations (MIC) ranging from 512 to 1024 μg/mL. According to the sampling technique used, results showed a different distribution of volatile compounds. Notably, thymol was found in lower amounts in the headspace—peak percentage areas below 5.27% (HS-SPME) and 0.60% (HS-GTS)—than in EOs (max. 48.65%), suggesting that its antimicrobial effect is higher in vapour. Furthermore, both headspace sampling techniques were proved to be complementary for the analysis of EO vapours, whereas HS-SPME yielded more accurate qualitative results and HS-GTS proved a better technique for quantitative analysis. 相似文献
47.
Hamidreza Enshaei Brenda G. Molina Luis J. del Valle Francesc Estrany Carme Arnan Jordi Puiggalí Núria Saperas Carlos Alemn 《Macromolecular bioscience》2019,19(8)
Ambroxol is a pharmacological chaperone (PC) for Gaucher disease that increases lysosomal activity of misfolded β‐glucocerebrosidase (GCase) while displaying a safe toxicological profile. In this work, different poly(ε‐caprolactone) (PCL)‐based systems are developed to regulate the sustained release of small polar drugs in physiological environments. For this purpose, ambroxol is selected as test case since the encapsulation and release of PCs using polymeric scaffolds have not been explored yet. More specifically, ambroxol is successfully loaded in electrospun PCL microfibers, which are subsequently coated with additional PCL layers using dip‐coating or spin‐coating. The time needed to achieve 80% release of loaded ambroxol increases from ≈15 min for uncoated fibrous scaffolds to 3 days and 1 week for dip‐coated and spin‐coated systems, respectively. Furthermore, it is proven that the released drug maintains its bioactivity, protecting GCase against induced thermal denaturation. 相似文献
48.
The early stage of secondary structural conversion of amyloid beta (Aβ) to misfolded aggregations is a key feature of Alzheimer's disease (AD). Under normal physiological conditions, Aβ peptides can protect neurons from the toxicity of highly concentrated metals. However, they become toxic under certain conditions. Under conditions of excess iron, amyloid precursor proteins (APP) become overexpressed. This subsequently increases Aβ production. Experimental studies suggest that Aβ fibrillation (main-pathway) and amorphous (off-pathway) aggregate formations are two competitive pathways driven by factors such as metal binding, pH and temperature. In this study, we performed molecular dynamic (MD) simulations to examine the initial stage of conformational transformations of human Aβ (hAβ) and rat Aβ (rAβ) peptides in the presence of Fe2+ and Fe3+ ions. Our results demonstrated that Fe2+ and Fe3+ play key roles in Aβs folding and aggregation. Fe3+ had a greater effect than Fe2+on Aβs’ folding during intermolecular interactions and subsequently, had a greater effect in decreasing structural diversity. Fe2+ was observed to be more likely than Fe3+ to interact with nitrogen atoms from the residues of imidazole rings of His. rAβ peptides are more energetically favorable than hAβ for intermolecular interactions and amorphous aggregations. We concluded that most hAβ structures were energetically unfavorable. However, hAβs with intermolecular β-sheet formations in the C-terminal were energetically favorable. It is notable that Fe2+ can change the surface charge of hAβ. Furthermore, Fe3+ can promote C-terminal folding by binding to Glu22 and Ala42, and by forming stable β-sheet formations on the C-terminal. Fe3+ can also pause the main-pathway by inducing random aggregations. 相似文献
49.
Poon TC Pang RT Chan KC Lee NL Chiu RW Tong YK Chim SS Ngai SM Sung JJ Lo YM 《Electrophoresis》2012,33(12):1894-1900
Previously, we reported that proteomic fingerprints were present in sera of patients with severe acute respiratory syndrome (SARS), and could separate patients into subgroups with different prognoses. In the present study, we examined the prognostic values of the SARS-associated proteomic features by biostatistical analysis, and deciphered the identities of those with prognostic values. Data of 20 SARS-associated serum proteomic features and ten serological variables from 38 SARS adult patients before treatment were subjected to multivariate logistic regression. Proteomic features of m/z 6634, m/z 7769, m/z 8635, and m/z 8865 were identified as independent prognostic markers. After purification by cation-exchange chromatography and gel electrophoresis, proteomic features of m/z 7769 and m/z 8865 were found to be platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) by tandem mass spectrometry, respectively. The associations of decreased serum PF4 and increased serum beta-TG levels with poor prognosis were confirmed by Western blot. Previous studies suggest that PF4 and beta-TG are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) in a negative and positive way, respectively. Our results suggest that PF4 and beta-TG may also play similar roles in the development of ARDS in SARS patients. 相似文献
50.
Haichao Zhu Meihua Liu Haiyan Li Ting Guan Qi Zhang Yang Chen Yingxiang Liu Rolf R. Hartmann Lina Yin Qingzhong Hu 《中国化学快报》2021,32(7):2327-2332
Exorbitant aldosterone is closely associated with various severe diseases, including congestive heart failure and chronic kidney disease. As aldosterone synthase is the pivotal enzyme in aldosterone biosynthesis, its inhibition constitutes a promising treatment for these diseases. Via a structure-based approach, a series of pyridyl substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-ones were designed as inhibitors of aldosterone synthase. Six compounds (5j, 5l, 5m 5w, 5x and 5y) distinguished themselves with potent inhibition (IC50 <100 nmol/L) and high selectivity over homogenous 11β-hydroxylase. As the most promising compound, 5x exhibited an IC50 of 12 nmol/L and an excellent selectivity factor (SF) of 157, which are both superior to those of the reference fadrazole (IC50 = 21 nmol/L, SF = 7). Importantly, 5x showed no inhibition against steroidogenic CYP17, CYP19 and a panel of hepatic CYP enzymes indicating an outstanding safety profile. As it manifested satisfactory pharmacokinetic properties in rats, compound 5x was considered as a drug candidate for further development. 相似文献